Complaint-to-ombudsman-over-EMA

Trusted evidence. Informed decisions. Better health.
Nordic Cochrane Centre
Rigshospitalet, Dept. 7811
Blegdamsvej 9
2100 Copenhagen Ø, Denmark
Tel: +45 35 45 71 12
Fax: +45 35 45 70 07
E-mail: general@cochrane.dk
10 October 2016
Complaint to the European ombudsman over maladministration at the European Medicines
Agency (EMA) in relation to the safety of the HPV vaccines
To: the European ombudsman
From:
Peter C Gøtzsche, DrMedSci, MSc, Director and Professor, the Nordic Cochrane Centre
Karsten Juhl Jørgensen, MD, DrMedSci, Deputy Director, the Nordic Cochrane Centre
Tom Jefferson, MD, Honorary Research Fellow, Centre for Evidence Based Medicine, Oxford, UK
Margrete Auken, MEP (The Greens/European Free Alliance)
Louise Brinth, MD, PhD, Danish Syncope Unit, Frederiksberg
Supported by:
The following people and organisations support the complaint to the EU ombudsman. They are not
responsible for the substance in the complaint, which it is up to the EU ombudsman to come to a
decision about.
Silvio Garattini, Director, Instituto di Ricerche Farmacologiche Mario Negri, Milano, Italy
Ralph Edwards, Ex-director, WHO Uppsala Monitoring Centre, Sweden
International Society of Drug Bulletins (ISDB)
Angela Spelsberg, Chair, Working Group on Health, Transparency International, Germany
No Gracias, Independent civil organization for transparency, integrity and equity, Spain
Juan Gérvas, Visiting Professor, National School of Public Health, Madrid, Spain
Ulrich Keil, Prof. Emer., Institute of Epidemiology and Social Medicine, Univ. of Münster, Germany
HealthWatch, a UK charity which promotes evidence-based medicine
Please note: This complaint to the ombudsman is not about whether the HPV vaccines do more
good than harm. It is about the EMA’s conduct, which we believe is an instance of
maladministration. It is possible that many of the serious harms that occur after vaccination are
autoimmune diseases. However, as we don’t know whether these diseases are caused by the HPV
vaccines, it must be a research priority to find out. The views we express here and our conclusions
are based on the facts we present; they are ours and not those of any organisation.
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Contents
Abbreviations ......................................................................................................................................................... 2
Summary of our complaint to the EU ombudsman ............................................................................................... 3
Outline of the case ................................................................................................................................................. 6
Our complaint to the EMA over the EMA’s handling of the possible serious harms of HPV vaccines .................. 6
Our complaint to the EU ombudsman ................................................................................................................... 8
Experience with the EMA related to two anti-obesity drugs ............................................................................. 9
The EMA’s general comments .......................................................................................................................... 11
The EMA’s comments on Brinth’s observations ............................................................................................... 16
Many redactions by the EMA in its documents are not legitimate .................................................................. 33
Uncertainties in the science that were left out of the official report ............................................................... 37
Conflicts of interest ........................................................................................................................................... 43
Final remarks..................................................................................................................................................... 54
Appendix. Correspondence related to the declaration of interests for the EMA’s executive director ............... 59
Abbreviations
AE: adverse event
CFS: chronic fatigue syndrome
CHMP: Committee for Medicinal Products for Human Use
CRPS: complex regional pain syndrome
DHMA: Danish Health and Medicines Authorities
DoI: declaration of interests
EMA: European Medicines Agency
FDA: Food and Drug Administration
HPV: human papilloma virus
LoQ: list of questions
MAH: marketing authorisation holder
PASS: post-authorisation safety study
POTS: postural orthostatic tachycardia syndrome
PRAC: Pharmacovigilance Risk Assessment Committee
SAE: serious adverts event
SAG: scientific advisory group
UMC: Uppsala Monitoring Centre
WHO: World’s Health Organization
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Summary of our complaint to the EU ombudsman
On 26 May 2016, we complained to the European Medicines Agency (EMA) over maladministration
at the EMA related to safety of the HPV vaccines. The EMA’s replies to us did not fully address our
concerns. Some of our concerns were not addressed at all, and several of the EMA’s statements
were either wrong or seriously misleading, or irrelevant for the criticism we had posed. We therefore
now complain to the EU ombudsman over the EMA. These are our most important observations:
1. The EMA has not been open and accountable to the citizens and has not respected their rights to
know about the scientific uncertainties related to the safety of HPV vaccines. The officially published
40-page report does not reflect the considerable disagreements among the EMA’s experts and
others but gives the impression of a unanimous rejection of the suspected harms.
2. The EMA has not lived up to the scientific standards that must be expected of the agency when
evaluating the science related to the safety of the HPV vaccines. One of the key arguments, which
appeared no less than ten times in the EMA’s official report, was that there was no difference
between what was observed and the expected background incidence of serious harms. However, the
underlying research was of such poor quality that these observations are virtually meaningless. The
EMA admitted that evidence from observed versus expected analyses cannot confirm a causal
association due to the inherent limitations in such data, but then, logically, the EMA cannot provide
any reassurance either for the opposite hypothesis, which is that the HPV vaccines are not harmful.
3. Contrary to the EMA’s statements, the official report does not describe the most relevant
evidence. The EMA emphasized research that is highly unreliable instead of focussing on the most
reliable research.
4. The amount of spin generated by EMA on its findings does not allow conclusion to be made. Its
official report could have been written by a PR agency working for a drug company. It is of public
interest to know who wrote or drafted the EMA’s official report, which is anonymous. The bottom
line for the EMA seems to have been that the vaccine should be protected from criticism at all costs
because it is believed to save lives. One pointer to this is that the text in the official report is nearly
identical to the assessments of the EMA’s rapporteur and the drug companies.
5. The EMA did not treat a Danish researcher who raised concerns about possible serious harms of
the HPV vaccines fairly. The EMA published pejorative comments that came close to an accusation of
scientific misconduct. The EMA’s comments were unprofessional, totally inappropriate and
represented unfounded criticism. If drug regulators behave like this when doctors report their
observations about possible serious harms of approved products, doctors will be unlikely to alert the
public to their observations in future, which would be a complete negation of one of the
cornerstones of pharmacovigilance.
6. The EMA seriously misrepresented the facts when it stated that its co-rapporteurs did not agree
with the Danish researcher about her concerns.
7. The EMA did not treat fairly the observations and concerns the Danish Health and Medicines
Authorities and the WHO Uppsala Monitoring Centre had raised about possible serious harms of the
HPV vaccines.
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8. Contrary to the EMA’s statements, the evidence was not assessed in an objective and scientifically
acceptable way and the evidence provided by experts was not given equal consideration. The
evidence provided by the vaccine manufacturers was generally accepted at face value, unlike the
more reliable and independent publications by the Danish researcher and her colleagues, the Danish
Health and Medicines Agency and the WHO Uppsala Monitoring Centre.
9. The extreme secrecy, with life-long confidentiality agreements, which the EMA imposed on its
working group members and scientific experts is not needed, is not legitimate and is not in the public
interest.
10. Some of the redactions the EMA imposed on the documents it delivered to the citizens according
to Freedom of Information requests were not needed, were not legitimate according to a 2010 ruling
by the ombudsman, and were not in the public interest. The illegitimate redactions included names
of contact people at the EMA and scientific assessors, case numbers of patients for which harms
were reported, country names for individual cases, numbers of reported harms for individual
countries, names of countries where there is an excess incidence of reported harms, and number of
doses of the vaccine used in individual countries.
11. Some of the experts that participated in the EMA’s working groups failed to declare their
conflicts of interest, and the EMA’s executive director, Guido Rasi, had not declared that he is the
inventor of several patents. We believe that, even if the inventor is not the owner of such patents,
they should be declared.
12. Contrary to the EMA’s statements, the EMA’s policy about restricting members of its Scientific
Advisory Group meeting to participate fully in the meeting was not correctly applied. For example,
there were no restrictions for the chair of the meeting, Andrew Pollard, although he had declared
several conflicts of interest in relation to the HPV vaccine manufacturers, while some of the
restricted people had no such conflicts of interest.
13. Contrary to the EMA’s statements, it is not correct that none of the EMA’s scientific committee
members and experts had any financial or other interests that could affect their impartiality. The
EMA used experts with financial ties to the manufacturers although it is always possible to find
experts without such conflicts. The names of some of the experts the EMA consulted were not
disclosed.
14. Contrary to the EMA’s statements, the review process was not transparent and independent; the
collective approach did not minimise the risk of bias; and the information presented by
pharmaceutical companies was not scrutinised and independently assessed. Nowhere in an internal
254-page EMA report is there any information that indicates that the data and analyses delivered by
the drug companies had been “thoroughly and critically reviewed,” the raw data re-analysed or even
just checked.
15. The scientific approach to finding possible harms of the HPV vaccines was insufficient. The drug
companies’ searches for possible harms in their own databases were grossly insufficient, and the
search strategies for the companies’ and the EMA’s searches in the published literature were not
revealed, and the EMA even redacted its search strategies. Such redactions make the EMA’s work
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not replicable and ultimately unaccountable, and may engender suspicion that the searches were
scientifically inadequate.
16. Contrary to the EMA’s statements, it is not a “very conservative approach” to let the drug
companies exclude a large amount of cases diagnosed by a skilled clinician without verifying by
inspecting the underlying raw data that this is legitimate. Furthermore, the EMA allowed one-fourth
of the vaccine trials to be omitted from the manufacturers’ review of the trials for unclear reasons
and did not review data from some of the trials in the holdings.
17. We believe it is illegitimate and not in the public interest that the EMA regards the drug
companies as the owners of data from clinical trials and data in their safety databases.
18. In all the vaccine trials apart from a small one, the so-called placebo was either not a placebo as
it contained aluminium adjuvant, which is neurotoxic in high doses, or it was another vaccine. This
makes it difficult to find a difference between harms of the vaccine and the “placebo,” but the EMA
failed to address this fundamental problem in its official report and allowed the manufacturers to
lump all the “placebo” data together. This is contrary to good scientific practice to such a degree that
we consider it outright scientific misconduct committed by the EMA.
19. We believe that the EMA’s interpretations of the numerous treaties, regulations and rules the
agency refers to are partly inconsistent and illegitimate, and not in the public interest.
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Outline of the case
Vaccines against the human papilloma virus (HPV) are likely to decrease deaths from cervical cancer,
as the incidence of precursors to cancer has decreased markedly after the vaccine was introduced.
In July 2015, the Danish Health and Medicines Authorities (DHMA) asked the European Medicines
Agency (EMA) to assess the research that had raised the possibility that the HPV vaccines in rare
cases might cause serious neurological harms. Prior to this, Denmark had contacted the European
Commission, and the Commission had requested the EMA to give its opinion.
In its submission to the EMA, the DHMA included peer reviewed articles published by PhD and
physician Louise Brinth from the Danish Syncope Unit at Frederiksberg Hospital in Copenhagen,
which had raised the hypothesis of a link between the vaccine and syncope and other neurological
events. The DHMA also included a review of the global data made by the Uppsala Monitoring Centre
(UMC, a WHO collaborating centre).
The prominent symptoms, which may be caused by the vaccines, are similar to those seen in socalled
functional disorders such as chronic fatigue syndrome (CFS) and they include postural
orthostatic tachycardia syndrome (POTS) and chronic regional pain syndrome (CRPS). The prevailing
hypothetical mechanism is an autoimmune reaction triggered by either the active component of the
vaccine or the adjuvant in the vaccine, or both. The syndromes are difficult to diagnose; their causes
are poorly understood; and they are likely to be substantially underreported. This complicates
studies of a causal link.
As we believed the EMA’s handling of the case constituted maladministration, we submitted a
“Complaint to the European Medicines Agency (EMA) over maladministration at the EMA,” dated 26
May 2016 (1).
Our complaint to the EMA over the EMA’s handling of the possible serious harms of HPV vaccines
On 26 November 2015, the EMA released a 40-page Assessment Report dated 11 November on the
safety of the HPV vaccines (2). This is the EMA’s official report (2), and it gives the impression of a
unanimous rejection of the suspected harms. However, only seven months earlier, the EMA had
concluded that, “A causal relationship between the dizziness and fatigue syndrome, Postural
Orthostatic Tachycardia Syndrome (POTS) and Gardasil [one of the HPV vaccines] can neither be
confirmed nor denied” (3). Moreover, there is an internal EMA report of 256 pages called “Briefing
note to experts” (4), which tells a very different story. This report, which provided the draft for the
EMA’s 40-page official report, is confidential but has been leaked to us in its original form, without
any redactions.
There are many problems with the EMA’s official report, and one of us, Louise Brinth, drew attention
to them in a 63-page document dated 15 December 2015 (5). When she wrote the document, Brinth
did not have access to the confidential internal report (4), only to the official one (2). We agreed with
Brinth’s criticism of the EMA, and our concerns about the EMA’s handling of the case increased
when we read the internal report. We therefore complained to the EMA over maladministration at
the EMA on 26 May 2016.
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In our complaint, we highlighted to the agency that according to Article 6 of the EU Treaty and the
Charter of Fundamental Rights of the European Union (6):
“Openness enables citizens to participate more closely in the decision-making process and
guarantees that the administration enjoys greater legitimacy and is more effective and more
accountable to the citizen in a democratic system. Openness contributes to strengthening the
principles of democracy and respect for fundamental rights.”
We asked the EMA to assess (1):
“A1. Whether the EMA has been open and accountable to the citizens and has respected their rights
to know about the uncertainties related to the safety of the HPV vaccines.
A2. Whether the EMA has lived up to the professional and scientific standards that must be expected
of the agency to guarantee that the administration enjoys legitimacy when evaluating the science
and the data related to the safety of the HPV vaccines.
A3. Whether the EMA has treated fairly - in a manner that guarantees that the administration enjoys
legitimacy - a Danish whistleblower, PhD Louise Brinth, when she raised concerns about possible
serious harms of the HPV vaccines.
A4. Whether the EMA has treated fairly - in a manner that guarantees that the administration enjoys
legitimacy - the observations and concerns the Danish Health and Medicines Authorities and the
Uppsala Monitoring Centre had raised about possible serious harms of the HPV vaccines.
A5. Whether the EMA’s procedures for evaluating the safety of medical interventions guarantee that
the administration enjoys legitimacy. The EMA asked the manufacturers of the vaccines to assess
potential harms of their own products in which they have huge financial interests.
A6. Whether the extreme secrecy, with life-long confidentiality agreements, which the EMA imposed
on its working group members and scientific experts, is needed; is legitimate; is in the public
interest; and guarantees that the administration enjoys legitimacy.
A7. Whether the redactions the EMA imposed on documents it delivered to the citizens according to
Freedom of Information requests were needed; were legitimate; are in the public interest; and
guarantees that the administration enjoys legitimacy.
A8. Whether the EMA has behaved in a manner that guarantees that the administration enjoys
legitimacy in relation to declaring conflicts of interest. We noticed a Guido Rasi’s name associated
with patents for inventions and wonder whether this is the same person who is the EMA’s director. If
so, we believe Rasi has failed to declare his conflicts of interest. We also believe that the rapporteur
for the EMA’s report, Julie Williams (2), has failed to declare her conflicts of interest.
A9. Whether the EMA behaves in a manner that guarantees that the administration enjoys
legitimacy when the agency use experts with financial ties to the manufacturers, in particular
considering that it is always possible to find experts without such conflicts.
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A10. In the interest of transparency, we urge the EMA to ensure that the names of all the experts
consulted are disclosed together with their conflict of interest declarations. We also urge the EMA to
ensure that the conflicts of interest statements from the rapporteur, the co-rapporteurs (Jean-
Michel Dogne (BE) and Qun-Ying Vue (SE)), their contact persons at the EMA and everyone else who
has given statements to the EMA are brought out in the open. Finally, we urge the EMA to ensure
that Declarations of Interests for officials at the EMA are honest.”
The replies we received from the EMA came in three parts:
On 17 June, Noël Wathion, EMA’s Deputy Executive Director, addressed conflicts of interest issues
related to Guido Rasi in a 2-page letter to Peter C Gøtzsche, which, among other things, stated: “The
Agency’s Executive Director Prof Rasi is indeed mentioned on a number of patents, even beyond
those referred to in footnote 15 of your complaint letter, but only as inventor, not as owner of the
patents” (7).
On 1 July, Noël Wathion sent the EMA’s response (17 pages) to the other issues we had raised, also
addressed to Peter C Gøtzsche only (8).
On 8 July, Carter-Ruck solicitors in London sent a 5-page letter, also addressed to Peter C Gøtzsche
only, marked “Private and confidential” on behalf of their client, Guido Rasi (9). According to this
letter, Rasi hoped that “you will agree immediately to amend the relevant passages of the
Publication [our complaint over the EMA], and to publish (in terms to be agreed) a suitable
statement of correction and apology withdrawing these false allegations.” This letter led to a long
correspondence, which we have reproduced in the Appendix, as we feel it has general interest.
Our complaint to the EU ombudsman
The EMA’s replies to us did not fully address our concerns. Some of our concerns were not addressed
at all, and several of the EMA’s statements were either wrong or seriously misleading, or irrelevant
for the criticism we had posed. We therefore complain to the European ombudsman as we still
believe the EMA’s handling of the HPV vaccines case is an instance of maladministration.
In its main reply to us (8), the EMA justified its decisions with reference to many regulations, rules,
guidelines and opinions. We don’t have confidence that the agency has interpreted these documents
in a way that ensures openness, gives the administration legitimacy, makes it accountable to the
citizens, and respects fundamental rights of access to information that is important for the citizens
when they make decisions about healthcare, as outlined in Article 6 of the EU Treaty and the Charter
of Fundamental Rights of the European Union (see above) (6).
The reason why we don’t have confidence in the way the EMA interprets and uses the rules is
especially - but not only - related to Regulation (EC) No 1049/2001 (6), which the EMA mentions six
times in its document to justify its actions. According to this regulation, a basic principle in the
European Union is to allow its citizens the widest possible access to the documents its agencies
possess. However, based on our previous experience with the EMA, we don’t have any confidence in
the way the EMA interprets this particular regulation. As this regulation is very important, we shall
explain in some detail what we experienced previously, which we described in the British Medical
Journal in 2011 (10). We believe that the EMA’s arguments in our earlier case are of considerable
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interest and relevance for the current case, which is also about possible serious harms of a medical
intervention.
Experience with the EMA related to two anti-obesity drugs
In 2007, researchers at the Nordic Cochrane Centre applied for access to the clinical study reports
and corresponding protocols for 15 placebo controlled trials of two anti-obesity drugs, rimonabant
and orlistat, which the manufacturers had submitted to the EMA to obtain marketing approval in the
European Union (10). The researchers explained that secrecy was not in the best interests of the
patients because biased reporting of drug trials is common and that they hadn’t found any
information that could compromise commercial interests in 44 trial protocols of industry initiated
trials they had reviewed previously.
Without any comment on the researchers’ arguments, the EMA replied that the documents could
not be released because it would undermine commercial interests. The researchers appealed to the
EMA’s then executive director, Thomas Lönngren, and asked him to explain why the EMA considered
that the commercial interests of the drug industry should over-ride the welfare of patients. The
researchers argued that the EMA’s attitude increased the risk of patients dying because their doctors
prescribed drugs for them without knowing what the true benefits and harms were. Lönngren
ignored their request for clarification and told them they could lodge a complaint with the European
ombudsman, which they did.
Over the following three years the EMA put forward several arguments to avoid disclosing the
documents: protection of commercial interests, no over-riding public interest, the administrative
burden involved, or the worthlessness of the data to the researchers after the EMA had redacted
them. The agency seemed not only to deliberately avoid allowing the researchers access with four
invalid arguments, but also to deliberately protract the process, as it did not respond to the
ombudsman’s letters before his rather generous deadlines had run out.
Protection of commercial interests was the EMA’s over-riding argument, but the agency seriously
misrepresented the facts, e.g. when it declared that it would undermine the protection of
commercial interests to allow access because the documents represented the full details of the
clinical development programme. There are no such details in these documents.
The researchers explained, among other things, that the clinical study reports and protocols are
based on well-known principles that can be applied to any drug trial; that the clinical study reports
describe the clinical effects of drugs; and that nothing in the EMA’s guidelines for preparation of
such reports indicates that any information included in them can be considered a trade secret. The
trial protocols are always sent to the clinical investigators, and it is unlikely that companies would
have left in any information that could be of commercial value.
The European ombudsman, P Nikiforos Diamandouros, noted that the risk of an interest being
undermined must be reasonably foreseeable and not purely hypothetical. He could not see that
access would “specifically and actually” undermine commercial interests. He inspected the relevant
reports and protocols at the EMA and concluded that the documents did not contain commercially
confidential information, in accordance with the researchers’ observations. He therefore criticised
the EMA’s refusal to grant them access.
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Even if commercial interests were undermined by disclosure, access would still have to be granted if
there was an over-riding public interest, which the researchers had argued was clearly the case. Antiobesity
pills are highly controversial. The effect on weight loss is small, and the harms are
substantial. People have died from cardiac and pulmonary complications or have experienced
psychiatric disturbances, including suicidal events, and most of the drugs have been deregistered for
safety reasons.
Despite the researchers’ convincing arguments, the EMA replied that it could not identify any overriding
public interest and remarked that the evaluation of safety and efficacy of drugs is its
responsibility. This argument was completely off topic, which was about whether the citizens should
have the possibility of seeing the facts for themselves and make up their own minds about the drugs.
There are countless examples where drug agencies have been far too slow to react to signals of
serious harm, and this relaxed attitude to drug safety has led to tens of thousands of deaths that
could have been avoided (11).
The ombudsman indicated that the researchers had established an over-riding public interest, but he
did not take a definitive stance on whether an over-riding public interest existed because this
question needed answering only if disclosure undermined commercial interests. He asked the EMA
to justify its position that there wasn’t an over-riding public interest, but the EMA avoided replying
by saying that the researchers had not given evidence of the existence of such an interest, although
they had done that. Furthermore, the EMA’s argument was irrelevant. A suspect asked for his alibi
on the day of the crime doesn’t get off the hook by asking for someone else’s alibi.
The EMA’s other arguments were also invalid. According to the EMA, the redaction of (unspecified)
“personal data” would cause the EMA a disproportionate effort that would divert attention from its
core business, as it would mean redacting 300,000-400,000 pages. In contrast, the Danish Drug
Agency had not seen the workload as a problem when it granted the researchers access to the
reports for a third anti-obesity drug, sibutramine, which was locally approved in Denmark (this drug
was taken off the market in 2010 for safety reasons). The 56 study reports the researchers received
comprised 14,309 pages in total, and in comparison, they requested only 15 study reports from the
EMA. If the EMA’s statement was not a lie, it came very close. It was totally impossible that 15 study
reports and its protocols could take up 300,000-400,000 pages. Rimonabant (Acomplia) was never
approved in the United States because of its serious harms, and its approval in Europe was
withdrawn by the European Commission on 16 January 2009 during the researchers’ complaint
proceedings with the ombudsman. When they ultimately received the reports they had requested
for the only remaining anti-obesity drug on the market, orlistat, there were only 7 trials and the total
amount of documentation was only 8,716 pages (12).
Of relevance for the HPV case is also the EMA’s argument that, “as a result of the redaction exercise,
the documents will be deprived of all the relevant information and the remaining parts of them will
be worthless for the interest of the complainant.” From what the researchers knew of clinical trial
reports and protocols it struck them as odd that they would contain so much “personal data” that
the documents became worthless. In contrast:
The ombudsman noted that the requested documents do not identify patients by name but by their
identification and test centre numbers, and he concluded that the only personal data are those
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identifying the study authors and principal investigators and to redact this information would be
quick and easy.
The EMA was completely resistant to the researchers’ arguments and those from the ombudsman.
However, after the ombudsman accused the EMA of maladministration in a press release on 7 June
2010 (13), three years after the request, the EMA reversed its stance. The EMA now gave the
misleading impression that it had favoured disclosure all the time, agreed with the ombudsman’s
reasoning, and noted that the same principles would be applied for future requests for access but
that it would consider the need to redact part of the documents.
The researchers received the data they requested from the EMA on 1 February 2011, which in some
cases included individual patient data in anonymised format, identified by individual and test centre
numbers.
The researchers concluded in their published paper about this affair (10) that, according to the
EMA’s responses to the ombudsman, the EMA put protecting the profits of the drug companies
ahead of protecting the lives and welfare of patients. They also noted that if the knowledge base is
incomplete, patients may suffer and cannot give fully informed consent when asked to participate in
trials, and that the EMA should be promoting access to full information that will aid rational decision
making, not impede it.
After his efforts at protecting the industry’s commercial interests, the EMA’s executive director,
Thomas Lönngren, quit the EMA. Although Lönngren had been told by the EMA that he should not
provide product-related advice to drug companies or take managerial, executive or consultative
positions in the industry for a period of 2 years, he became director of a new company, Pharma
Executive Consulting Ltd, in November 2010 while still employed by the EMA (14).
The EMA’s general comments
The EMA’s main letter to us (8) started with general comments, which we have numbered below for
ease of cross-referencing in the remainder of the text.
B1. The EMA noted: “the benefits will have to (continue to) outweigh any risks associated with HPV
vaccines. Therefore, any additional data which moves up the evidence base is important to further
substantiate the benefit/risk balance. EMA, therefore, is somewhat surprised that - different to your
previous approach - you appear to now overestimate the value of studies that have important
limitations such as lacking a comparator group” (8, p1).
In our view, this is an irrelevant remark. Our complaint is not about whether the vaccines do more
good than harm, or whether they cause the alleged harms, but about the EMA’s conduct.
Furthermore, the EMA makes an undue and erroneous assumption, just like it did about Brinth (see
item C1 below). Needless to say, none of us have changed our approach to science and we do not
overestimate the value of studies that have no control group. The limitations of randomised trials for
assessing rare harms, and the necessity for observational studies in this context, are well-known in
the scientific community. It is inappropriate for an EU agency to make such assumptions about
people who criticise them. The EMA should stick to the facts and should not engage in guess-work.
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B2. The EMA’s statement that, “the use of HPV vaccines is expected to prevent many cases of
cervical cancer” is also irrelevant for our complaint, but it says something important about the EMA.
This is exactly how the drug industry argues: don’t worry about the harms, as our drugs prevent
many deaths.
B3. The EMA stated that the review process is transparent and independent; that the collective
approach minimises the risk of bias (p1); and that “stringent legal and regulatory safeguards are in
place to ensure that any information presented by pharmaceutical companies is scrutinised and
independently assessed” (p2).
We do not agree that the information presented by pharmaceutical companies was scrutinised and
independently assessed; it was generally taken at face value. The assessors based their judgements
on aggregate data provided by the manufacturers; they did not check the manufacturers’ results,
verify the appropriateness of excluding reports of suspected harms, carry out independent analyses,
or access the raw data of the trial datasets presented in the responses by the manufacturers (15).
There is no trace of re-analyses in the documentation. This is a fundamental failure, as the
companies have a huge vested interest in NOT finding the possible harms in their databases, and as
we assume the EMA knows that drug companies should not be trusted (11,16).
We also believe that the collective approach was not one that “minimises the risk of bias.” If
anything, consensus committees increase the risk of bias, as they often have one or two dominant
people with strong views. In fact, according to information available to us, those who expressed
concerns about vaccine safety at the Scientific Advisory Group (SAG) meeting on 21 October 2015
were pressurised by the leaders to agree to the so-called consensus. That is not science but politics.
We will return to this problem under item C5.2 below.
B4. “Any evidence is assessed in a factual, scientific and objective way. These high standards were
adhered to in the EMA handling of the safety of HPV vaccines. All the evidence provided by experts,
which constituted a significant element of all data assessed, was given equal consideration and this
included the publications of Dr Louise Brinth and colleagues, the Danish Health and Medicines
Agency and the Uppsala Monitoring Centre” (p2).
We find that the evidence was not assessed in an objective and scientifically acceptable way, and it
was not given equal consideration. For example, the co-rapporteurs were overruled by the
rapporteur and their divergent opinions were left out of the official report (4). The data provided by
the marketing authorisation holders (MAHs) were generally taken at face value, in contrast to the
much more reliable independent research carried out by Brinth. There were also subjective,
unfounded and erroneous allegations about Brinth's research whereas the limitations of the
randomised trials related to detection of rare events and the use of active substances as “placebo,”
were not taken into account (see items C1 and C9 below).
B5. “The published report cannot contain all the data that the scientific committee looks at, it is a
comprehensive summary of all the data assessed, which highlights the most relevant evidence in
support of the scientific committee's conclusions” (p2).
It is misleading to say that the official report describes the most relevant evidence. The EMA’s
confidential report of 256 pages (4) tells a story about uncertainty related to whether the HPV
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vaccines can cause serious harms, and it also contains serious criticism of the EMA’s procedures and
the conclusions made, by both the co-rapporteurs, other experts and the DHMA. Relevant evidence
in support of the criticisms was not included in the official report (see below). In contrast, the official
report sends the message that “everybody agrees that there is nothing to worry about,” which is also
exactly how the Danish media interpreted the EMA’s report. The same day the EMA’s report came
out, a major Danish newspaper brought the headline: “Danish researchers demolished: no relation
between the HPV vaccine and serious symptoms,” and the article even insinuated that Brinth and
her group had committed scientific misconduct (17).
We believe the public has a fundamental right to know that there are uncertainties, which can be
important for their decisions about medical interventions, and that the EMA through its
inappropriate actions, rather than protecting the whistleblowers that raised a suspicion of serious
harms caused by the vaccine, ignited a public witch hunt on the Danish researchers. Hiding
disagreement and uncertainty about harms of the vaccine may fuel distrust rather than foster it.
B6. “EMA makes all available information that its [sic] holds accessible upon request. Before release
of any such documents, EMA has to ensure to meet its legal duty to protect the privacy of clinical
subjects and any commercially confidential information. This means that wherever necessary some
information will be redacted to protect individuals as well as intellectual property.”
It seems to us that the EMA has “forgotten” the ombudsman’s ruling in our previous case. The
ombudsman remarked in 2010 that since the requested documents did not identify patients by
name but by their identification and test centre numbers, the only personal data to redact were
those identifying the study authors and principal investigators (10). However, as we explain below
(under items D1 to D8), the EMA redacted far more than this in the HPV case.
B7. “EMA's approach to conflicts of interests [sic] is a balanced approach aiming to effectively
restrict the involvement of experts with possible conflicts of interests [sic] in the EMA's work while
maintaining EMA's ability to access the best available expertise. We would like to confirm that the
declarations of interests and curriculum vitae of all experts are published on the EMA's website in
the interest of transparency and to foster trust in the regulatory system.”
We believe this is not correct. Among the core members of the SAG were Margareta Blennow and
Anders Lindberg who appeared on the list of SAG members we received from the EMA on 9 June
2016 (18), but we could not find any conflicts of interest declarations for these two people on the
EMA’s website when we checked it in May 2016. See further discussion of this issue under item F2
below.
B8. “The need for life-long confidentiality can by no means be compared to an imposition of life-long
secrecy as it does not prevent experts who disagree with a collegial decision to discuss their
disagreements in public, provided that they shall make clear that the views expressed are their own
and not those of the concerned scientific committee, and that they do not disclose commercially
confidential information.”
This statement is misleading. In the EMA’s 256-page internal report (4), there is a “Confidentiality
Reminder” on page 2:
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“As an EMA expert you are bound to life-long duty of confidentiality. The duty of confidentiality
applies to all information of the kind covered by the obligation of professional secrecy. This includes,
for example, the fact that there is a meeting, that you have been nominated to participate, the
agenda of the meeting, the product or company concerned, the participants, any part of the
discussions and outcome. All documentation (correspondence, reports, minutes, etc.) must be kept
as confidential and stored in a secure place or destroyed. The duty of confidentiality stops only if
information has been made public and only to the extent that has been released into the public
domain.”
This is not a permission to discuss disagreements in public; it amounts to a gagging clause. According
to information we have, the members of one of the EMA’s committees clearly felt that this
amounted to a life-long prohibition to speak in public about disagreements. We have also been told
that a person who posed critical questions was reminded of the life-long confidentiality.
Furthermore, the EMA’s misleading post hoc statement has a safeguard. People are not allowed to
disclose commercially confidential information, but since the EMA, just as the drug industry, defines
what they mean by “commercially confidential information”, which changes over time (10,19), we
doubt that anyone would dare speak out in public even now, after the EMA’s post hoc statement.
How would these experts know what the EMA currently considers confidential?
B9. “We would like to stress that transparency is at the heart of EMA and that EMA has been at the
forefront of efforts to continuously increase transparency about medicines regulation; we believe it
helps to ensure that the general public receives the necessary information to make informed
decisions.”
This is not correct. As explained above, the EMA did everything it could to prevent us from getting
access to the clinical study reports on two anti-obesity drugs in its possession until it was forced by
the ombudsman to reverse its stance in 2010 (10). Further, after 2010, the EMA has tried to wind the
clock back to its culture of extreme secrecy. In the AbbVie case, the EMA redacted much information
in 2014 that, in the ombudsman’s opinion, did not require redacting, e.g. the rationale for dosage
selections; the considerations used in determining sample sizes for clinical trials; and text relating to
protocol changes (19). Prior to this, in the spring of 2013, AbbVie had dragged the EMA into the
European Court because of its new openness policy, and at a meeting in Brussels later the same year,
AbbVie incensed European drug regulators by making it clear that it regarded clinical trial data on
adverse events as confidential information that it was entitled to keep to itself (20).
In 2014, the EMA suggested a “peeping Tom” policy. No one would be allowed to download
redacted reports, and they could be viewed on screen only (taking photos of the screen pictures
would also be prohibited, according to information we received at a meeting at the EMA back then);
some statistical analyses could be commercially confidential; safety and efficacy data about off-label
prescribed drugs could be kept out of third party view; researchers would have to contractually
agree that third parties (i.e. pharmaceutical companies) would have direct legal claims under UK law
against them for possible violations of the Terms of Use; infractions to the cumbersome procedural
limits could thus not only be punished by withdrawal of access but appeared also to open up the
possibility of spurious lawsuits over “misuse of data” that essentially would silence critics (21). The
EMA’s 2014 proposals would have made relevant research about drug safety virtually impossible and
they caused a public outcry including a protest from the EU’s ombudsman (22). In two responses, the
EMA’s executive director Guido Rasi defended the agency’s draft policy, explaining that the EMA’s
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latest draft policy represented “absolutely no change in direction.” It surely did, and the EMA had to
backpedal (22).
B10. “We trust that the information and clarification provided has adequately addressed the points
raised in your letter and we hope that our response supports EMA as a scientific body that is open
and accountable to EU citizens” (p3).
The EMA is far from being an agency that is “open and accountable to EU citizens” and the EMA’s
reply to our complaint did not increase our confidence in the agency.
B11. “Once a safety referral is initiated, the EMA Pharmacovigilance Risk Assessment Committee
(PRAC) 3 , which carries out the assessment, nominates from among its members so-called (Co)-
Rapporteurs who take the lead in the scientific assessment and who have the task of thoroughly
assessing the data and draft their recommendations which is then shared with all PRAC members ...
As a first step, the PRAC prepares a list of questions (LoQs), which is sent to the marketing
authorisation holders (MAHs), and should be answered within a certain timeframe depending on the
urgency of the matter” (p4).
“In case a scientific advisory group (SAG) is held the preliminary assessment reports are shared with
the SAG as part of the Briefing Note. In case of the HPV vaccines the SAG Vaccines was convened,
which is a standing group of leading experts in the field of vaccines and vaccine safety. It was created
in 2012 ... Its composition is fixed but on a case by case basis it can be complemented with ad hoc
experts (non-core members) in a particular disease or with expertise on an issue for which the
committees requested advice” (pp4-5).
“For any of the steps, the assessment reports set out only the preliminary conclusions of the (Co)-
Rapporteurs at that point in time. These reports in no way bind the PRAC to its final conclusions,
which take into account the views expressed by all PRAC members, the uncertainties identified
during the procedure and responses to scientific questions posed by the PRAC, and are developed on
the basis of the overall body of evidence available at that moment” (p5).
“The PRAC reached its scientific recommendation by consensus following plenary discussion. This
recommendation was presented in the final PRAC assessment report which summarised all the data
assessed by the committee in support of the PRAC conclusions. The PRAC recommendation was
subsequently forwarded to the Committee for Medicinal Products for Human Use (CHMP) who
issued its opinion following a review and a plenary discussion. Finally the Commission Decision was
issued by the European Commission and the referral procedure was concluded.”
We have several concerns with this. The (Co)-Rapporteurs are crucial for the validity of the whole
scientific process as they are those who “take the lead in the scientific assessment and who have the
task of thoroughly assessing the data and draft their recommendations.” As they are the ones who
know best, it is concerning that they were consistently overruled by the Rapporteur when she had
another opinion, which invariably favoured the view that the suspected harms were not related to
the vaccine (4). It is also concerning that in an area with so much uncertainty, “The PRAC reached its
scientific recommendation by consensus following plenary discussion.” It is very common in group
work that one or two people dominate the process and that its outcome may therefore reflect more
what these 1-2 people think than the disagreeing views that existed in the group (see our note about
15

the leaders pressurising those who expressed concerns about vaccine safety under item B3 above).
Science is the antithesis of “consensus,” and scientists did not arrive at the laws of nature by a
consensus process.
We are also concerned that the consensus “recommendation was presented in the final PRAC
assessment report which summarised all the data assessed by the committee in support of the PRAC
conclusions.” This looks like cherry-picking. What about all the data and evidence-based criticism
that did NOT support the PRAC conclusions (see our comment under item B5 above)? Apparently, if
we compare the internal report with the published report, the relevant criticisms seem to have
disappeared. Our final concern is that, although the (Co)-Rapporteurs were supposed to thoroughly
assess the data, they didn’t do this. They accepted most of what they got from the drug companies
at face value (see items B3 and B4 above).
“It has to be noted that all the documents generated during the review are considered confidential
during the course of the procedure. However, they are available upon request (via the access to
documents route) once the procedure has concluded and the European Commission has issued its
final decision” (p5).
As noted under items D1 to D8 above, some documents are so extensively redacted that they may
be useless for certain research purposes.
The EMA’s comments on Brinth’s observations
We use below the same numbering as we used in our complaint to the EMA over the EMA (1).
C1. The EMA asserted in its published report (2, p24) that: “Overall, the case series reported by
Brinth and colleagues (2015) is considered to represent a highly selected sample of patients,
apparently chosen to fit a pre-specified hypothesis of vaccine-induced injury.” In our complaint to
the EMA (1), we noted that Brinth stated in her report (5, p17) that she and her co-workers included
all consecutively referred patients, with the exception of those that met the exclusion criteria. We
found that the EMA’s allegations constitute guesswork (“apparently”), are pejorative and come close
to an accusation of scientific misconduct. We furthermore noted that the EMA’s comments are
totally inappropriate for an EU authority to make on honest researchers and that the EMA’s criticism
was totally unfounded.
In its reply, the EMA explained that “the methodology of case series has important limitations as it
lacks a comparator group and is also known to be vulnerable to selection bias ... another example is
the potential of misinterpretation of data due to the likelihood of recall bias, which is something
inherent to the methods used, and is partly driven by patient awareness. EMA respectfully disagrees
with your claim that ‘EMA's allegations constitute guesswork (‘apparently’), are pejorative and come
close to an accusation of scientific misconduct’. EMA's position, as discussed above, is not based on
‘guesswork’ but rather objective considerations. Moreover, nothing in the EMA's position is either
intended to or may be construed as pejorative or an accusation of any type of misconduct” (pp5-6).
The EMA is evasive. Its discussion about bias is irrelevant and it is clear from Brinth’s research that
she was aware of this risk and had pointed out the well-known limitations of the research design.
Further, it is NOT an objective consideration to say about a researcher that she used a “highly
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selected sample of patients, apparently chosen to fit a pre-specified hypothesis of vaccine-induced
injury.” Brinth felt that this comment was defamatory.
C2. The EMA asserted in its published report (2, p23) that, “many of these symptoms would require
some sort of objective clinical evaluation, yet there is no information on how this was done or what
other clinical assessment may have been undertaken to exclude other causes of the symptoms.”
Brinth noted that nausea, headache, abdominal pain and fatigue are subjective symptoms that
escape “objective clinical evaluation,” and that orthostatic intolerance was quantified through tilttesting,
which constitutes more than “some sort of objective clinical evaluation.” Brinth furthermore
noted that the evaluation of her work as presented by the EMA in its official report is based on many
assumptions, most of which she believed were wrong. She was also concerned that the EMA report
did not include the complete data set, and that it was not defined how the included parts were
chosen. She found that this had resulted in several inconsistencies between the representation of
the Uppsala Monitoring Centre (UMC) data in the original DHMA report and the EMA report (5,
pp25-26). Brinth furthermore noted that her observations and hypotheses were supported by the
independent review of the global data made by the UMC (5, p26).
In our complaint to the EMA, we noted that we found that the EMA’s comments about Brinth’s
research were unprofessional, misleading, inappropriate and pejorative, and that the EMA’s
approach involved cherry-picking, which is unscientific. We noted that the Uppsala centre had
received more reports of potential harms from the HPV vaccines than reports of similar harms from
all other vaccines offered to women. We also noted that although both EMA reports mentioned the
finding by the UMC that a substantially higher proportion of case reports were classified as serious
for the HPV vaccines compared to other vaccines, no attention was paid to this in either of the EMA
reports (2,4).
In its reply to us (p6), the EMA noted that the imbalance in the absolute numbers of reports of
POTS/CRPS with HPV versus non-HPV vaccines was not statistically significant. We cannot comment
on this, as we have not seen the statistical analyses. However, we find it relevant to reiterate that
the EMA paid no attention to the fact that the cases were more serious for the HPV vaccines than for
other vaccines. We also note that Brinth wrote that there were a number of important and relevant,
potential side effects, which were statistically significantly over-reported with the HPV vaccine, but
which the EMA failed to mention: disturbances in consciousness, muscular weakness, disability
issues, and neurological signs and symptoms (5, p29).
We have discussed these issues with key people at the UMC, Ralph Edwards and Rebecca Chandler.
They considered that their data were disregarded much too easily by the EMA and without adequate
justification, given that it meant ignoring a large number of seriously affected patients with
prolonged significant disability and admission to hospital from consideration of whether serious
harm is caused by the vaccine, even at the hypothesis stage. They regard the EMA report as
inadequate and worryingly dismissive. They have now published a paper with more data and
arguments that strengthen their suspicion that the HPV vaccines may cause serious harms (23). They
reported that the combination of headache and dizziness with either fatigue or syncope was found
to be more commonly reported in HPV vaccine reports compared with non-HPV vaccine reports for
females aged 9-25 years. This disproportionality remained when those countries reporting the
signals of CRPS (Japan) and POTS (Denmark) were excluded.
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C3. The EMA asserted in its published report (2, p27) that the chronic fatigue syndrome has “been
reported relatively constantly since 2009.” Brinth noted that, according to the UMC report, the
chronic fatigue syndrome has “been increasing since 2012 with a marked increase between 2012 and
2013” (5, p27). In our complaint to the EMA, we noted that we believed that the EMA had
misrepresented the UMC report with regard to possible serious harms of the vaccine.
In its reply (p6), the EMA stated that it may have been misunderstood and that “the phrase ‘Chronic
fatigue syndrome (CFS) has been reported constantly since 2009’, means that the event has been
continuously recorded over a period of time and does not contain a judgement on the intensity of
the reporting.”
However, the text in the EMA’s published report was: “Fibromyalgia, CFS and ME/PVFS have been
reported relatively constantly since 2009 (with a slight decrease in 2011/12), but reports of POTS and
CRPS had notably increased since 2013.” The EMA misrepresented these facts in its reply to us.
Firstly, although using quotation marks, the EMA provided a misquotation when it left out
“relatively” and “(with a slight decrease in 2011/12).” Secondly, and more important, a text that says
that something has increased, and then decreased, and that something else has been reported
relatively constantly, cannot be misunderstood.
C4. The EMA failed to mention not only that the Danish reports were more often classified as
“serious” but also that they had more often included a large amount of clinical, relevant information
than reports from other countries. Instead, the EMA mentioned that “the terms POTS, orthostatic
intolerance and autonomic nervous system imbalance are reported disproportionately more in HPV
reports from Denmark vs HPV reports in other countries” (2, p27). Brinth drew attention to the fact
that the UMC had noted that a significantly greater proportion of the reports from Denmark were
considered “good reports;” were classified as “serious;” and were received from either a physician, a
consumer or a lawyer (5, p28).
We found that the EMA, rather than praising the Danish diligence, cast doubts on whether the
Danish peer reviewed research should be believed. We noted that this is an inappropriate attitude to
safety for a drug agency to have and that we agreed with Brinth that the EMA had misrepresented
the UMC review in its own report, thereby creating the impression that Brinth should have published
substandard research. The EMA had furthermore omitted some of the important suspected harms of
the vaccine.
In its reply (p6), the EMA stated: “Regarding your comment about discrepancies between EMA and
the Danish reports in the way adverse events were classified please note that the PRAC has used the
GVP definition of serious adverts events (SAEs) in order to classify the adverse events: ‘An adverse
reaction which results in death, is life-threatening, requires in-patient hospitalisation or prolongation
of existing hospitalisation, results in persistent or significant disability or incapacity, or is a congenital
anomaly/birth defect’. Most symptoms of CRPS and POTS are non-specific, meaning that they are
difficult to diagnose both in the general population and in vaccinated individuals and some
symptoms may overlap with chronic fatigue syndrome (CFS). Many of the reports of POTS
considered in the referral have features of chronic fatigue syndrome and some patients have been
diagnosed with both POTS and chronic fatigue syndrome, an observation which was also supported
by recent publications (Brinth et al, 2015). Indeed, reports of other symptoms/signs were also taken
into consideration, provided that there was a suspicion of POTS or CRPS in line with the scope of the
18

eferral. For this analysis, reports that did not fully meet the diagnostic criteria for these syndromes
were also considered also taking into account underreporting. A very conservative approach was
used including also reports that may not have been true POTS or CRPS under the definitions. Even
with this approach no link to the vaccines could be identified. One element that emerged clearly
from this assessment is that individual cases did not show a consistent pattern regarding time-toonset
following vaccination or clinical characteristics.”
We find the EMA’s reply highly misleading. It is not a “very conservative approach” to let the drug
companies exclude a large amount of cases diagnosed by a skilled clinician without verifying by
inspecting the underlying raw data that this is legitimate, see item C7 below.
C5. Brinth had the impression that the minutes from the EMA meetings were not released and might
not be publicly accessible either, and she found it unclear which data people reviewed at the
meetings. She also criticised the EMA’s published report for giving the impression that all the experts
had agreed, which she called a false consensus based on the participants being bound to secrecy,
particularly as she did not believe that two single scientists would share exactly the same views in a
matter as complex as this. She found it “a very strange, unscientific and undemocratic approach” (5,
p33).
We informed the EMA that we agreed with Brinth and that the EMA’s official 40-page report (2) is
misleading, as it gives people the impression that there is nothing to worry about in relation to
vaccine safety and that the experts consulted by the EMA agreed on this. We also noted that the
EMA’s confidential, internal report (4) revealed that several experts were uncertain and called for
further research, but that there was nothing about this in the official report. Finally, we noted that
the extreme level of secrecy - life-long - imposed by the EMA on its working group members and
other experts was inappropriate and went against the public interest in openness and transparency
about possible serious harms of the vaccine.
The EMA’s reply to us on this point was very long, and we have therefore divided it up in seven parts.
C5.1. The EMA stated that, “the SAG Vaccines was consulted on specific questions that the PRAC put
to them. The SAG does not release any minutes document after its meeting, however both the PRAC
questions and the SAG responses are inserted verbatim in the PRAC assessment report published on
the EMA web site 5 ” (p7).
This is not transparent. Does the phrase “The SAG does not release any minutes document after its
meeting” mean that minutes are not taken? Or does it mean that minutes were taken but not
released, in which case it is relevant to know whether they are confidential or whether the public
can get access to them. We asked the EMA about the minutes and received 6 pages labelled
“Confidential” (24) where several names had been redacted (see item D7 below).
C5.2. The EMA stated that, “Divergent views are only reflected in the document where consensus
cannot be reached on a given question. In the case of the HPV vaccines referral, all SAG experts who
were allowed to contribute without restrictions endorsed the final responses by consensus.”
This statement documents that even though the EMA involved a scientific advisory group (SAG), the
EMA does not focus on science but on politics. When people sit in a room together and know that it
19

is expected of them that they reach consensus, it is not surprising that consensus is actually reached.
Those who have differing views will feel a pressure to agree with the majority, and it is well-known
from countless studies in psychology that such group pressure and group think can make people
agree to things that directly contrasts with what they actually think about the subject. Science is
about encouraging people to air their different interpretations of the data openly, as this is how
science is best advanced; it is the very heart of science. In our view, the EMA’s processes, which lead
to secrecy about differing views, mean that the EMA does not enjoy legitimacy. As the EMA’s most
important work is to assess the benefits and harms of drugs, it is to be regarded as a scientific
institution. The EMA is NOT a policy setting body, but that is how it behaves.
C5.3. The EMA noted: “As regards your comment that ‘the minutes of the [EMA] meetings are not
released’, this is incorrect: documents held by EMA are either proactively published on our website
(including minutes of CHMP and PRAC meetings) or released in response to requests for access to
documents, subject to the exceptions set out in Article 4 of Regulation (EC) No 1049/2001. This also
applies to documents from SAGs. EMA cannot, therefore, agree that ‘this [is] a very strange,
unscientific and undemocratic approach.’”
The EMA consistently quotes Article 4 of Regulation (EC) No 1049/2001 when they talk about NOT
giving the public full access to documents. It seems to us that the EMA has chosen to ignore what
this regulation is about. It is NOT about introducing secrecy and obstacles, in fact quite the opposite.
It is about openness, and according to this regulation, a basic principle in the European Union is to
allow its citizens the widest possible access to the documents its agencies possess. If the EMA
genuinely wanted to be open and transparent, it would have provided a list of all available
documents in the HPV vaccine case alongside its official 40-page report on its website. The EMA
could even have made all the documents easy to download, perhaps after redaction of a few names,
which would have been quick and easy to do (10). Instead, the EMA did the opposite. It is not
possible for citizens to request documents when they have no idea about which documents exist,
and it requires immense detective work to try to find this out. The life-long obligation to secrecy in
relation to the EMA’s scientific meetings contrasts sharply with the practice at its US counterpart,
the Food and Drug Administration, where such meetings are open to the public and sometimes
available by webcast.
C5.4. The EMA stated: “As the European Commission asked the PRAC in the Notification letter
whether any other measures needed to be considered, it is the responsibility of the PRAC, the (Co)-
Rapporteurs, and all the members to discuss this question and give its opinion. The PRAC specifically
asked the SAG Vaccines to discuss the feasibility of performing further studies with the potential to
provide robust and meaningful results within existing data sources in Europe. The response from the
SAG Vaccines is included verbatim in the PRAC assessment report 7 as mentioned above. The SAG
response does not preclude any other research centre, academic institute or national authority from
conducting its own studies, should they decide to do so. It should be noted that it is outside of EMA's
(or its committees) remit to recommend public health authorities to conduct (or not) research
studies in any field.”
We feel that this is not an explanation but an evasive statement. The EMA could - and should - have
concluded that more research was needed because of the current uncertainty. This has nothing to
do with recommending any particular institution or authority to do such research.
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C5.5. “The EMA respectfully disagrees with your opinion that a life-long obligation for professional
secrecy imposed on experts participating in EMA working groups and scientific advice groups is
‘extreme’, ‘absurd’, illegitimate and contrary to public interest and undermining the legitimacy of the
EMA. The professional secrecy obligation is set forth in Article 76 Regulation (EC) No 726/2004,
which governs the activities and functioning of EMA. This obligation is imposed on EMA staff,
members of the EMA Management Board, members of EMA scientific committees and experts,
including experts who are members of SAGs and ad hoc expert groups established to provide
scientific advice experts views in relation to ongoing regulatory procedures, such as the HPV referral
in question.”
We find that the EMA’s explanation above is in direct contrast with what the EMA stated earlier in
their reply to us, namely that “The need for life-long confidentiality can by no means be compared to
an imposition of life-long secrecy as it does not prevent experts who disagree with a collegial
decision to discuss their disagreements in public” (see item B8 above). We also fail to understand
what the difference should be between “life-long confidentiality” and “life-long secrecy” and the
EMA does not explain why it distinguishes between the two. We furthermore wonder how it is
possible for the EMA to issue two contrasting explanations that seem impossible to reconcile.
C5.6. The EMA noted: “Article 76 explicitly provides that the obligation for professional secrecy
applies ‘even after their duties have ceased’. This Article reflects the more general secrecy obligation
imposed on all EU officials, including EMA staff, by Article 339 of the Treaty on the Functioning of the
European Union not to disclose information of the kind covered by the obligation of professional
secrecy, even after their duties have ceased. The above confidentiality obligations are transposed
and further clarified by Article 17 of the ‘Regulations and Rules applicable to officials and other
servants of the European Union (Staff Regulations)’ and the ‘EMA Guidance on Confidentiality and
Discretion’ (Section 3 of the EMA Code of Conduct)” (p8).
The EMA’s mentioning of numerous treaties, regulations and rules cannot justify that the EMA is
inconsistent when it interprets them. The EMA cannot have life-long secrecy and freedom for its
experts to speak out at the same time.
C5.7. The EMA stated: “However, we argue that there are two common sense exceptions to the
above rule: a) the relevant information may become public at some point in time and the secrecy
obligation would thus become devoid of its purpose; b) the experts who disagreed with a collegial
decision may discuss their disagreement in public, provided that they make clear that the views
expressed are their own and not the view of the committee and that they do not disclose
commercially confidential information. This last remark should hopefully address your observations
concerning ‘a life-long secrecy clause that prevents them [the experts] from discussing their
disagreements in public.’”
This is certainly not how the experts interpreted the gagging clause they were presented with on
page 2 of the 256-page internal document (see the text under item B8 above). If the EMA really
meant what they wrote, then why then did the EMA not tell its experts that this was the case? Why
wasn’t this important information made explicit in the rules for the committees?
C6. In her “responsum,” Brinth noted: “Reading EMA’s report it seems to me that the review of the
safety data which includes available data from the clinical trials and post-marketing surveillance and
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the literature review was all collected by the marketing authorization holders (MAHs)
[GlaxoSmithKline Biologicals, Merck Sharp & Dohme Limited, and Sanofi Pasteur MSD]? This must
have been in the form of a report written by the MAHs to the EMA? Is this report freely available?”
(5, p34).
We wrote to the EMA that we found it “unacceptable that the EMA in its official report (2) did not
make it clear that it allowed the drug companies to be their own judges (4) when evaluating whether
the vaccine is safe, particularly since there is a huge amount of money at stake: The global
expenditure so far on HPV vaccines can be roughly estimated at €25 billion. The EMA asked the
companies to search for side effects of the vaccine in their own databases and did not check the
companies’ work for accuracy. This is not an acceptable procedure. There are countless examples of
drug companies hiding serious - even lethal - harms from the authorities (6) [not the current
reference 6].”
The EMA replied that, “The MAHs are the owners of data from clinical trials and data in their safety
databases; these data are crucial in any assessment and cannot be ignored. For any referral
procedure the data submitted by the pharmaceutical companies will always be assessed by the (Co)-
Rapporteurs who then do their own assessment, may ask additional questions or pose requests for
further analysis/data to the MAHs. This is described in the Q&As documents regarding referral
procedures. As mentioned above, in case of the HPV referral, the responses to the LoQs from the
PRAC were submitted by the MAHs to all PRAC members. In the questions, the MAHs were asked
specifically to analyse the data and provide an evaluation of the results” (p8).
We disagree with the EMA’s statement that the drug companies are the owners of clinical trial data
and the ombudsman also seemed to disagree when he, in 2010, called it maladministration that the
EMA would not give us access to such data (10). The statement tells us that the EMA is primarily
concerned with protecting the drug companies’ commercial interests rather than protecting the
patients. There was no doubt about this when Thomas Lönngren was the EMA’s executive director
(10), and there seems to be little doubt about it today when Guido Rasi is the executive director.
Patients run an unknown risk by volunteering to participate in clinical trials, and without this altruism
and sacrifice for the common good, there would be no drug trials. Therefore, clinical trial data
belong to the patients, in fact to every one of us. The drug companies have caused tremendous
harms by withholding trial data, arguing that they are their property and commercially confidential.
The withholding of trial data has resulted in millions of patients losing their lives unnecessarily
because their doctors did not know how dangerous the drugs were that they prescribed to them,
and it is a major reason that our prescription drugs are one of the leading causes of death, after
heart disease and cancer (11,16).
The EMA cannot protect the drug companies’ commercial interests and the patients against drug
harms at the same time. Currently, we consider the EMA dysfunctional and lacking legitimacy when
it states that the drug companies are the owners of clinical trial data. It is about time that the agency
sided with patients.
As we have stated above under items B3 and B4, the companies’ analyses and interpretations seem
to have been taken mostly at face value, which is not a scientific approach. The EMA stated that,
“For any referral procedure the data submitted by the pharmaceutical companies will always be
assessed by the (Co)-Rapporteurs who then do their own assessment, may ask additional questions
22

or pose requests for further analysis/data to the MAHs.” We find this statement misleading in
relation to the HPV case, as few questions were asked (4; search for “Assessor’s comment”) and as
the (Co)-Rapporteurs did not seem to have assessed the data, but simply believed them. Throughout
the whole document where the EMA provides replies to our complaint over the EMA, the EMA refers
to procedures and tells us what might have happened according to these procedures. We also find
this misleading. We made concrete observations in our complaint to the EMA but instead of replying
in a similarly concrete way, the EMA doesn’t tell us what actually happened, only what ideally might
have happened. This is not openness and it is not the type of argument that would be allowed in a
court case. A person who has broken the law will not get off the hook by saying that according to the
law it is not allowed to break the law.
The EMA also stated: “The data submitted by the MAHs is only one part of the data assessed by the
Committee. A search of the EudraVigilance database and the published literature were also
conducted independently by EMA and by the assessing teams, and have been discussed thoroughly
during the procedure. It may be noted that some of the data may overlap, for example
EudraVigilance may contain individual case safety reports submitted by MAHs, as well as others. All
data reviewed by the PRAC can be made available to the public following requests for access to
documents, as per the EMA policy” (p8).
We shall comment on the EMA’s and the MAHs’ literature searches under item C11 below.
C7. Brinth found it highly problematic that readers of the EMA reports – and particularly herself in
her capacity of a medical professional having diagnosed and evaluated a substantial part of the
Danish cases – did not have access to the EMA’s case detection methods. Since a substantial
proportion of the POTS cases reported as suspected side effects from Denmark had been examined
by her, she found it troubling and strange to see that POTS cases had been overruled by MAHs/EMA
and judged as not meeting or only partially meeting the diagnostic criteria in 50 out of 83 cases given
the diagnosis POTS in the Adverse Events Reports (AERs). She interpreted the EMA’s published
report (2) as meaning that it was the MAHs that had evaluated the AERs and noted that she and her
co-workers had used the exact same criteria as those mentioned in the EMA’s report when they
diagnosed POTS, and that they had been quite restrictive in their diagnostic practice. Brinth wanted
to know whether the MAHs had based their evaluation on the AERs alone, or whether they had been
through the whole medical record for these patients. She noted that it is well known that an AER will
not include all the details of the clinical history and that it is therefore rare that any spontaneous
report will meet the diagnostic criteria. She also noted that the WHO (the Uppsala Monitoring
Centre) had stated that the Danish AERs did not in the essence differ from reports from the rest of
world – but were of a higher quality (5, pp34-35).
We wrote to the EMA stating that we found it unacceptable that no one - not even the person
whose research was so strongly (and unfairly) criticised in the EMA’s official report (2) - can judge on
what grounds and by whom 50 out of 83 cases of POTS were dismissed by the EMA. We also noted
that the secret internal EMA report (4) revealed that the POTS cases were dismissed without having
access to the full medical records; that the “research” carried out by the drug companies clearly did
not live up to accepted standards for such research; and that the EMA did not ensure that it did. We
found this very serious because the EMA used the companies’ assessments to overrule the research
done by Brinth, which is of a much higher standard and publicly available.
23

We furthermore noted to the EMA, with reference to the PRAC co-rapporteur’s referral updated
assessment report (25, pp9-10) that the Danish Health and Medicines Authorities (DHMA) had also
strongly criticised the EMA’s approach: “The main conclusion in the Danish report is not, as
described in the assessment, to change focus to CFS. Rather the review highlights the necessity to
evaluate combinations of symptoms rather than only performing separate evaluations of individual
diagnoses. It shows that although the number of POTS cases is very high in Denmark, compared to
the rest of the world, the symptom pattern seen in the Danish dataset is similar to reports submitted
from other countries. Even though it cannot be shown for certain at this point, it is likely based on
these data, that patients with the same symptomatology would receive different diagnoses in
different member states e.g. POTS in DK and CFS/ME in others. This consideration is important for
the discussion of consistency regarding the POTS signal, where it is stated that the finding of the
majority of POTS cases in Denmark does not support a causal relationship. We do not agree with this
conclusion based on the data.”
Immediately after this, the DHMA stated under Risk Management Plan/ Post-authorisation Safety
Studies/ Conditions: “Need for further studies regarding the signal for POTS: We agree with the
conclusion from the rapporteurs and also state in the Danish report [this shows that these
comments come from the DHMA], that the data from spontaneous reports cannot be used to
provide evidence for a causal relationship between symptoms and vaccination. However in view of
the methodological limitations of the data available and the fact that the observed cases did exceed
the expected cases, especially in Japan and Denmark, the conclusions should be cautious and the
signal cannot be dismissed either based on the current evidence. We recommend that the vaccine
SAG and expert meeting include a discussion of the need and possibilities to design appropriate PASS
studies [post-authorisation safety studies] to explore POTS further. Similar question as Q3 regarding
CRPS.”
In their reply to us, the EMA stated: “All PRAC members had the opportunity to comment in writing
during the commenting phase ... Rapporteurs for the referral, assessors and other members of the
PRAC attended the SAG Vaccines meeting in person and had the opportunity to ask any questions to
participants, including to pharmaceutical companies” (p8).
Again, the EMA avoided answering our serious concerns. The EMA describes what might have
happened according to the rules, but not what did happen, which may have been very little or
nothing. We have found no data, for example, suggesting that any important questions were asked
to the drug companies at the SAG meeting.
The EMA also wrote: “It needs to be emphasised that every decision taken by the PRAC - and this is
the case for any EMA committees - is a collective decision. This can be reached by majority if there
are members that do not agree with the majority conclusions, or by consensus. Members that do not
agree with the majority conclusions have to justify the grounds for their divergent position, which
are then made public. In this case the PRAC recommendation was adopted by consensus, and any
questions or outstanding issues were resolved, which is why the procedure could conclude” (p9).
This “explanation” is meaningless. Considering the considerable disagreements that existed at all
levels in this process, not least the serious criticism from the DHMA (only available in the EMA’s
internal report (4)) that originally raised the concerns about possible serious harms of the HPV
vaccines and asked the EMA to look into this, we wonder why nothing about these disagreements
24

was made public. We also note the strong hold the EMA has on the consensus committee. People
are not likely to express disagreement with the majority, as they would then be exposed publicly. It
is much easier to swallow what comes on the table, even if you disagree with it. But this is the
opposite of science. What came out of this meeting, we would call a cosmetic consensus.
The EMA wrote to us: “The MAHs' review of post-marketing reports was based on data from the
MAHs' pharmacovigilance databases, which include spontaneous reports from healthcare
professionals and consumers. It is common practice that when a report is received, the MAH
contacts the reporter and tries to retrieve as much medical information as can be shared. However,
access to full medical records is not usually granted by treating physicians to manufacturers of
medicinal products. A wide strategy to identify potential cases was employed, in addition to
identifying reports with an established diagnosis of POTS or CRPS (see also response to point 8
below).”
The fact that 50 out of 83 cases of POTS were dismissed by the MAHs and subsequently also by the
EMA (see just above, under this item) shows beyond any doubt that neither the MAHs, nor the EMA,
did their work properly.
C8. Brinth wrote that the EMA’s official report noted on page 12 that PRAC requested the MAHs to
search not only “for reports specifically containing the terms POTS and CRPS” but also to use
“common search strategies” to identify possible cases of undiagnosed CRPS and POTS. Brinth said
that it would have been relevant to have these search strategies clearly defined and given because,
to the best of her knowledge, there are no common search strategies which have been previously
defined for either POTS or CRPS (5, pp35-36).
We wrote to the EMA that we agreed with Brinth. It is notoriously difficult to identify the harms in
question and it is unacceptably poor standards for such research not to define precisely what the
search strategies were. It is a fundamental requirement for systematic searches that the
combination of search terms is clearly described so that the searches can be reproduced by others
(26). In the EMA’s internal 256-page report, however, we found some search strategies the
companies had used when searching in their databases (4, pp29-31). We find these search strategies
vastly insufficient. As just one example, the Uppsala Monitoring Centre has reported that for the
largest clusters they identified in the WHO VigiBase(R), the most commonly reported AE terms were
headache and dizziness and fatigue or syncope (23). They also found that the combination of
headache and dizziness with either fatigue or syncope was found to be more commonly reported in
HPV vaccine reports compared with non-HPV vaccine reports for females aged 9--25 years. The
MAHs did not search for headache and they did not combine the terms in the way the Uppsala
centre did. “Dizziness” needed to occur together with either “orthostatic intolerance” or “orthostatic
heart rate response increased” in order to count, and there were other restrictions that must have
led to many cases being overlooked. The EMA nonetheless uncritically reproduced the incidence
rates of CRPS and POTS constructed by the manufacturers (15).
In its reply, the EMA “acknowledged that POTS is characterised by a constellation of symptoms. The
PRAC noted that most symptoms of CRPS and POTS are unspecific, making them difficult to diagnose
both in the general population and in vaccinated individuals. The PRAC report clearly states that in
order to identify possible cases of undiagnosed CRPS and POTS, the MAHs were requested to use
common search strategies, which also used an algorithm to identify reports with combinations of
25

signs and symptoms common in CRPS or POTS, even if the reports did not include an established
diagnosis of POTS or CRPS. This strategy is meant to retrieve more cases, not fewer, which is the
conservative approach used in pharmacovigilance. There seems to be a misunderstanding in Brinth's
statement and in the comment from the requester: the word ‘common’ is used in the report as
‘shared by two or more people or things’, not as ‘occurring, found, or done often,’ i. e. the search
strategies were shared between the MAHs to enable the comparison of data.”
The EMA’s reply is worrying. The EMA agrees with us that cases are hard to find in searches and
speaks about a conservative algorithm, which is supposed to find many cases. But they don’t tell us
what this algorithm is. As just stated, we found these algorithms (4), which were bound to miss many
relevant cases. Further, as already noted, it can hardly be called a “conservative approach” when the
method ended up discarding most of Brinth’s carefully documented cases. Finally, the meaning of
the EMA’s many semantic subtleties continues to escape us. We do not understand what the EMA
tries to tell us with its explanation of the word “common.”
The EMA wrote to us: “The clinical details of all reports were individually evaluated by the MAHs to
determine if the established criteria of CRPS and POTS were fulfilled, and then reviewed by the (Co)-
Rapporteurs. The MAHs were asked to clearly describe case detection methods and discuss whether
the reported cases fulfilled published or recognized diagnostic criteria. In the case of POTS the
Sheldon and colleagues (2015) 8 publication and that of Raj (2013) 9 were used for the case definition.
During the review of the data provided by the MAHs, the (Co)-Rapporteurs assessed case detection
methods for each MAH. Further details on the broad, common search strategies are included in the
(Co)-Rapporteurs' assessment reports, previously released and available upon request” (p9).
Essential issues in science should not be ”available upon request.” As just noted, we found two vastly
insufficient algorithms used by the MAHs in the EMA’s internal report and they also appear in an
assessment report (25, pp24-26). A colleague provided us with a copy of “Rapporteurs’ Day 150
Joint Response Assessment Report” from November 2014, which was an assessment of Gardasil 9
from Sanofi Pasteur MSD on behalf of the EMA (27). Although not being part of the EMA procedures
we complain about here, it is nonetheless highly relevant for our complaint. The rapporteurs were
concerned that Sanofi had avoided identifying possible cases of serious harms of the vaccine and
their concerns were supported by the GCP [Good Clinical Practice] Inspection report (27, p79 and
p101):
“The reporting procedure for AEs [adverse events] in this trial was complicated by the fact that as
per protocol there was only specific, short, AE reporting periods in connection to each vaccination. In
between, any new symptoms were only to be reported as ‘new medical events’ … The information
available about new medical events was however limited, as only symptoms were collected and no
further medical assessments were made and no outcome was recorded. The reporting of SAEs
[serious adverse events] was also not required during the full course of the trial ... in the inspectors’
opinion it is not an optimal method of collecting safety data, especially not systemic side effects that
could appear long after the vaccinations were given ... A potential concern is that there are 3
subjects in the clinical safety database who have been diagnosed with POTS, an on-going safety
concern for the quadrivalent Gardasil, after receipt of Gardasil 9 and that in none of the 3 cases was
the event of POTS reported as an AE ... Furthermore, for case AN29076, the Applicant should
describe the rationale for inclusion of POTS as ‘new medical history’ instead of an AE given the
report that it occurred 24 days post dose 1. For case AN71508, the Applicant should explain why the
26

hospitalisation for severe dizziness which occurred prior to the end of study visit was not reported as
an SAE ... The Applicant should discuss, in the specific terms of case 37083, why the term
‘dysautonomia’ was not included on the line listing.”
Again, this shows that the EMA’s confidence in the work of the MAHs is totally misguided. The
following example also involved Sanofi Pasteur MSD. When the DHMA in 2014 asked Sanofi Pasteur
MSD to review its database for potential side effects of its HPV vaccine, the company searched for
POTS in a way that made the number of cases retrieved very low (28). This was discovered by the
Danish National Board of Health, partly because only 3 of 26 Danish reports of POTS showed up in
the company’s searches. Sanofi Pasteur MSD had been asked to search on a number of specific
symptoms including dizziness, palpitations, rapid heart rate, tremor, fatigue and fainting, but the
company ignored these clear orders. Instead, Sanofi Pasteur MSD searched on three symptoms:
“postural dizziness”, “orthostatic intolerance” and “palpitations and dizziness." As terms used in
reports of harms are the ones used by the doctors reporting them, unusual search terms will yield
few results. Just like the two algorithms did.
Interestingly, Brinth noted in her “responsum”: “We use the exact same criteria” (those by Sheldon
and Raj) (5, pp34-35), but many of her cases were nonetheless dismissed by the drug companies and
subsequently by the EMA.
C9. Brinth noted that the EMA’s question 2 to the companies did not make any sense to her because
both the vaccine group and the control group received aluminium adjuvanted “placebo” or another
aluminium adjuvanted vaccine as “placebo.” She wondered why the EMA instructed the companies
to only discuss potential explanations if a difference was observed. Brinth interpreted this as
meaning that the EMA took it for granted that we knew with a very high degree of certainty that side
effects due to the adjuvant would not be found (5, p37).
We told the EMA that we agreed with Brinth. In all the vaccine trials apart from a small one, the socalled
placebo was not a placebo as it contained aluminium adjuvant, which is neurotoxic in high
doses. It is therefore difficult to find a difference between harms of the vaccine and the “placebo,”
but the EMA failed to address this fundamental problem in its official report (2). It is clear from the
EMA’s internal report (4) that the MAHs simply lumped the results from trials with a genuine placebo
with those that had a potentially neurotoxic “placebo": “Clinical safety data. For the purpose of the
referral, the MAH was requested to provide an in depth review of the CRPS and POTS cases observed
within all clinical studies. To respond to this request, the MAH has pooled the safety data from 18
completed and unblinded studies designed with an active comparator group (either placebo or
another vaccine other than an HPV vaccine, i.e. Hepatitis B, Hepatitis A) which includes a total of
42,047 vaccinees (21,268 in HPV group and 20,779 in comparator groups)” (4, p119 in the pdf, or
7/67 in the subdocument). We believe this constitutes scientific misconduct, but the EMA accepted
it, without reservations: “Strength of the potential association. The few cases reported from RCTs
[randomised clinical trials] are evenly distributed between the qHPV and placebo groups which does
not suggest an association” (4, p20 in the pdf, or p11 in the subdocument).
The EMA noted in its response to us: “For both Cervarix and Gardasil, all studies submitted for the
marketing authorisation application were placebo controlled. Placebo consisted in most studies of
aluminium-containing solution or of a hepatitis B vaccine (Recombivax HB, used in Gardasil
development) or a Hepatitis A vaccine (Havrix, used in Cervarix development). Study 018 for Gardasil
27

investigated almost 700 subjects using an inactive placebo. The study's primary objective was to
evaluate the safety of Gardasil among 9- to 15- year-old boys and girls. This study allowed the
comparison of Gardasil with a non-aluminium-containing placebo (all other studies compared the
vaccine with aluminium containing placebo, as mentioned). Subjects were also evaluated for new
medical conditions 1 year post vaccination. The data from study 018 was compared with the safety
of the antigens and adjuvant as evaluated in the rest of the clinical trials. Overall there was no
significant increase in the reactogenicity following Gardasil vaccination as compared to the nonaluminium
containing placebo administration” (pp9-10).
We wonder if the EMA knows what a placebo is. The EMA called all studies placebo controlled, even
those that use an active vaccine as “placebo,” and accepted the analyses from the MAHs where they
had lumped results obtained with a genuine placebo with those with something that was NOT a
placebo. These active “placebos” could have similar side effects as the HPV vaccines, which would
make it difficult or impossible to use the trials to find out if the HPV vaccines cause the suspected
rare harms. We accused the EMA of scientific misconduct, but the EMA didn’t respond to the serious
issues we raised. The information the EMA provided is irrelevant for our complaint. Seven hundred
people in a trial with a genuine placebo are clearly far too little to detect rare harms from a vaccine
or a difference between trials that use saline injections and active comparators.
The EMA wrote to us: “For both vaccines development, the use of AI(OHh (5001Jg) rather than a true
placebo (inactive control) was found acceptable by the CHMP in order to maintain the double
blinding of the studies and consequently the validity of data ... The approach taken for both vaccines
was found by the CHMP as a reliable way to establish the safety profile of the vaccines at the time of
authorisation” (p10).
We do not agree. The data are NOT valid for an evaluation of the possible harms of the vaccine when
the control group is being treated with a potentially neurotoxic aluminium-containing solution. And
we are not reassured by the EMA’s statement that, “On the basis of the scientific assessments
performed over the years by EMA 10 and other experts such as from EFSA 11 , FDA 12 and WHO 13,14 , the
scientific evidence available to date continue to support the safe and effective use of aluminium
adjuvants in vaccines”. Drug regulators have all too often been wrong when they assured the public
that there was nothing to worry about (11,16). Finally, the EMA did not explain what it meant by
“maintain the double blinding of the studies and consequently the validity of data.” This statement
could be interpreted as implying that aluminium salts are so reactogenic that an inert placebo would
cause far fewer reactions (systemic or local) and lead to quick identification of active substance
recipients. If this is what the EMA means, it then also means that trials with “an active placebo”
cannot be used to evaluate possible harms of the vaccines. Further, the outcome of primary interest
in the trials is cervical cell changes, the assessment of which in routine practice is unlikely to be
influenced by lack of blinding. The priority to maintain blinding while losing the possibility to
investigate harms of the vaccines therefore raises concerns about EMA procedures.
The EMA wrote to us: “Concerning POTS and CRPS, in the review of clinical trial data done for the
referral, a total of 60,594 subjects were included for Gardasil/Silgard and Gardasil 9 and 42,047
subjects for Cervarix. No cases of POTS or CRPS were identified in the Cervarix and comparator
cohorts. The incidence of POTS and CRPS in the Gardasil/Silgard and Gardasil 9 clinical trials was less
than 1 case per 10,000 person-years and comparable in the Gardasil/Silgard/Gardasil 9 and
corresponding placebo cohorts, showing that, irrespective of the comparator used, the incidence of
28

POTS and CRPS was very low in the vaccinated group and in line with the estimated incidence of
POTS and CRPS in the general unvaccinated population.”
The clinical trials have been conducted and analysed by the drug companies, which have a huge
interest in NOT finding any serious problems with their vaccines. In addition, we know that these
conditions are vastly underdiagnosed and that it is therefore intensely misleading to compare the
incidence in trials with the “estimated incidence of POTS and CRPS in the general unvaccinated
population.” Finally, many more people are needed than those enrolled in the trials to detect if the
vaccines cause very rare harms. The EMA disregards the fact that only 700 of these many patients
were randomised to a genuine placebo.
The EMA did not ensure that all relevant trials were included in the assessments (15). The criteria for
including trials are unclear (4), which one of the assessors commented on (4, pp 28-29 or 19-20 in
pdf). The wording suggests that only data from useful trials were included, i.e. only those used to
apply for licensing (4, pp 28-29 or 19-20 in pdf). For the qHPV vaccine, for example, the follow-up
combined denominator (the total number of females) from trials presented by Merck Sharp &
Dohme was 44,793 (15). Cross referencing the HPV vaccine trial numbers with the EMA trial holdings
revealed that the EMA does not hold clinical study reports for these trials: V501-007, V501-011,
V501-018, V501-020, V501-024, and V501-025 (15). The total number of females in these trials is
11,542. This means that the EMA cannot have possibly checked one-fourth of the manufacturers’
dataset (11,542/44.793 = 25.7%). Conversely, at least four trials listed in the EMA’s qHPV holdings
(or that are known to the EMA) are not included in the manufacturer’s list (15).
C10. Brinth criticised the EMA for asking the MAHs to provide an analysis of the observed number of
post-marketing cases of CRPS and POTS in association with their HPV vaccine in comparison to those
expected in the target population. Brinth argued that the analysis should discuss the assumptions
made with respect to the background incidence in the target population and also the influence of
potential under-reporting of cases in association with HPV vaccines. Brinth also noted that it is not
possible for the time being to give a reasonable estimate of the background incidence “of these very
underrecognized, underdiagnosed and poorly understood disease entities with very different
diagnostic practices applied depending on nationality, medical specialty etc” (5, p39).
We agreed with Brinth and wrote to the EMA that one of the key arguments in the EMA’s report (2)
was that there was no difference between what was observed and the expected background
incidence. We explained that this observation was meaningless, as the underlying research was of
very poor quality: “For example, for some of the analyses, the observed incidence of chronic fatigue
syndrome was used to estimate the expected incidence of POTS (4, p96, or 87 in subdocument).
Furthermore, the EMA writes in its report that for POTS with the Gardasil/Silgard vaccine, the
observed number of cases was generally lower than expected under almost all assumptions for all
regions and countries except for Denmark (2, p17). This observation should have alerted the EMA to
the fact that analyses based on expected incidence are grossly unreliable. We find it curious and
scientifically unacceptable that the official EMA report (2) puts more weight on the ‘observed versus
expected’ analyses produced by the companies than the much more reliable Uppsala data.”
The EMA’s reply to us on this key issue was highly disappointing. The agency “acknowledged that the
calculation of the background incidence rate in the relevant age population is difficult” and that
“PRAC also acknowledged that given the complexity of the syndrome and likely differential practice
29

in approaches to diagnosis and management across countries and centres, reported background
incidence may differ between countries.” Both the Belgian and the Swedish co-rapporteurs were
highly critical of the observed versus expected analyses: “For both CRPS and POTS, the Co-
Rapporteur considers that Observed vs expected methodology used in this CRPS analysis is based on
many assumptions, which cannot be verified” (4, p210 or 31/77) and “The recalculation is therefore
not considered helpful to reach the overall conclusion. The proposed recalculation of observed
versus expected ratios is therefore not endorsed by CoRapp SE” (25, p9). Even the rapporteur was
critical of these analyses: “Evidence from OE analyses cannot confirm a causal association due to the
inherent limitations in spontaneous data” (4, p215 or 36/77).
However, the EMA’s official report does not reflect this substantial doubt about the trustworthiness
of observed versus expected analyses (2). Quite the contrary. In no less than ten places in the 40-
page report are these analyses used to convince the readers of the report that they should not worry
about possible serious harms of the HPV vaccines:
“Observed versus expected (O/E) analyses cannot determine causality, but they are useful in signal
validation and, in the absence of robust epidemiological data, in preliminary signal evaluation” (p13).
“The O/E analyses are generally reassuring” (p14).
“The analysis of O/E cases suggests that the number of observed POTS cases is low compared to
those expected. The analyses are generally reassuring” (p15).
“The results of the O/E analysis for Gardasil/Silgard showed that the observed counts were less than
expected in most scenarios of under-reporting, case definitions and risk periods” (p16).
“The results of the O/E analyses for POTS with Gardasil/Silgard showed that the observed number of
cases was generally lower than expected under almost all assumptions for all regions and countries
except for Denmark” (p17).
“The O/E analysis showed that the number of spontaneous reports of chronic fatigue following
Cervarix vaccination was consistent with estimated background rates even assuming low reporting”
(p31).
"Taking into account the O/E analyses, which do not suggest an increased occurrence of CRPS or
POTS in relation to the HPV vaccines ...” (p37).
“Overall, the comparisons of observed versus expected number of spontaneous reports do not
suggest an increased occurrence of CRPS in relation to the HPV vaccines” (p38).
“Overall, comparisons of observed versus expected number of spontaneous reports, with the same
scenarios as described above for CRPS, do not suggest an increased occurrence of POTS in relation to
the HPV vaccines” (p38).
“The PRAC considered that the observed versus expected analyses took into account a wide range of
scenarios regarding underreporting and included reports that did not fully meet the diagnostic
criteria for the syndromes. Overall, in these analyses the rates of these syndromes in vaccinated girls
were consistent with expected rates in these age groups” (p39).
When “evidence from OE analyses cannot confirm a causal association due to the inherent
limitations in spontaneous data” then, logically, they cannot provide any reassurance either for the
opposite hypothesis, which is that the HPV vaccines are not harmful. We also wonder why the EMA
put far more weight on analyses they admit are doubtful in its internal reports but not in its official
report, than on much more reliable data produced by an independent researcher. The EMA put so
much spin on something that doesn’t allow any conclusion to be made that we feel it could have
been written by a PR agency working for a drug company. We therefore would like to know who
30

wrote or drafted the EMA’s 40-page official report. No authors are listed on the report, which is
another example of the lack of transparency and accountability and a possible attempt at sheltering
behind the concept of corporate responsibility.
This does not foster public confidence in the EMA’s impartiality.
The EMA wrote that, “The approach taken in this referral procedure by applying the observed versus
expected analysis allowed the PRAC to use the most sensitive detection of a possible excess of the
natural background rates and account for a range of possible under-reporting up to 99%. It should be
noted that the PRAC took into account the data from Uppsala Monitoring Centre (UMC) report
accordingly” (pp10-11). Brinth had argued that the analysis should discuss the assumptions made
with respect to the background incidence, and we had agreed, but the EMA did not give us these
assumptions but merely noted that they took account of possible under-reporting up to 99%. As we
cannot check the analyses and the assumptions they are based on because we don’t have access to
them, we cannot comment on the EMA’s postulates. Further, it is easy to say that the PRAC took the
UMC data into account but we don’t know how this was done.
C11. Brinth wrote that the EMA had asked the MAHs to provide a critical appraisal of the strength of
evidence for a causal association between the HPV vaccine and CRPS and POTS considering the
published literature (including epidemiological studies) and the possible causes and pathophysiology
of CRPS and POTS, and to discuss whether there is a biological basis for a possible causal association.
She wanted to know if this appraisal was performed by the MAHs only or supplemented by the EMA
and highlighted that it would be highly relevant to know the search strategies applied in the
literature research. She also mentioned that the current perception in the scientific field is that POTS
is probably associated with autoimmunity, and that publications were starting to emerge that
confirmed this view, and that autoantibodies are also found in CRPS and ME/CFS [myalgic
encephalomyelitis/chronic fatigue syndrome] (5, p39).
We told the EMA that we found it totally unacceptable to perform a literature review without giving
the readers details of its methods, in particular the search strategies used. This is the corner stone
for such research, which is clear from manuals about systematic literature reviews, e.g. the Cochrane
Handbook (26). We also found that the EMA had dismissed the research performed at the Danish
Syncope Unit in a way that was unfair, misleading, partly erroneous and pejorative. We believe that
if drug regulators behave like this when doctors report their observations about possible serious
harms of approved products, doctors will be unlikely to alert the public to their observations in
future. We consider that this would be a tragedy for public health.
The EMA’s reply to us on this crucial point was very disappointing: “A literature review was
conducted by the EMA and in addition by the Rapporteur's teams; the publication search criteria
used included the names of the syndromes and the presence of either the mention of the words
‘vaccine’ or ‘HPV’, with associated synonyms.” We had just pointed out to the EMA that it is totally
unacceptable to perform a literature review without giving the readers details of the methods, in
particular the search strategies used. Despite this, the EMA did not disclose any search strategy. This
makes us suspect that the searches were scientifically inadequate, since, as the dictum goes: “If you
have nothing to hide, then hide nothing.” We have been unable to find the EMA’s search strategies
in any of the reports in our possession. The closest we came was this (29, pp62-64):
31

p62
p63
p64
This speaks for itself. The EMA’s approach to literature searches is not only unscientific but the
agency seems to be secretive about simple principles of methods. We doubt the EMA can provide
any justification for redacting its search methods but would like to know why they were redacted.
Redactions such as these make the EMA’s work not replicable and ultimately unaccountable.
The MAHs’ literature searches were grossly inadequate. When searching for CRPS, “The keywords for
the search included ‘complex regional pain syndrome’ or ‘pain syndrome’ and ‘quadrivalent HPV
vaccine’ or ‘Gardasil’” (4, p58) and when searching for POTS, “Keywords included ‘POTS’ or
‘tachycardia’ or ‘postural orthostatic’ and quadrivalent and 9-valent Human Papillomavirus vaccine
(qHPV and 9vHPV)” (4, p69).
The EMA disagreed with our interpretation that, "the EMA had ridiculed and dismissed the research
performed at the Danish Syncope Unit in a way that was unfair, misleading, partly erroneous and
pejorative” with this argument: “As already mentioned above, limitations of the studies should be
mentioned even when those are innate shortcomings of the methodology used. EMA's position is
objective and based on scientific evidence. Nothing in the EMA's position is either intended to or
may be construed as pejorative” (p11). The EMA’s argument actually confirms that its description of
Brinth’s research is “unfair, misleading, partly erroneous and pejorative” since, contrary to what the
EMA just asserted once again, Brinth DID mention the innate shortcomings of the methodology she
used in her research. This was to such an extent that an independent researcher has concluded that
Brinth’s research is clearly above the usual standard for such research (30).
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Many redactions by the EMA in its documents are not legitimate
Various people have obtained redacted documents from the EMA through Freedom of Information
requests, which they have shared with us. As we have access to the unredacted version of the EMA’s
confidential 256-page internal document (4), we can see which bits the EMA redacted. In our
complaint to the EMA, we gave six examples of redactions that we found unreasonable (our
comments are in brackets), reproduced here in their entirety:
D1. Names of contact people at the EMA for the rapporteur and co-rapporteurs. (This does not make
sense, particularly since the names for the rapporteur and co-rapporteurs were not redacted).
D2. Case numbers of patients for which harms were reported. (This is not necessary, as it is not
possible to identify individual people from a case number, but it can make it difficult to assess a
scientific report when such numbers are missing).
D3. Country names for individual cases. (This does not make sense unless the idea is to obscure for
outsiders whether or not the EMA’s assessments are trustworthy, particularly since the EMA
considers the Danish cases to be dubious).
D4. Numbers of reported harms for individual countries, names of countries where there is an excess
incidence of reported harms, and number of doses of the vaccine used in individual countries. (This
is even more difficult to understand unless the idea is to obscure for outsiders whether or not the
EMA’s report is trustworthy and whether or not the EMA’s criticism of the Danish Syncope Centre is
warranted).
D5. While it is indicated that some harms reports come from the Danish Syncope Centre, it is
redacted that the centre is located at Frederiksberg Hospital. (This does not make any sense,
particularly not when the name of the hospital was not redacted elsewhere).
D6. The publication identifier for an article in press. (This is pretty meaningless unless the idea is to
keep readers of the report in the dark. Scientists routinely refer to papers in press and it should not
be hidden where such papers will appear).
D7. Even more curious than the above redactions is the following: In the minutes from the SAG
meeting on HPV vaccines on 21 October 2015 (24), the EMA had redacted not only what seemed to
be 6 of 7 names of EMA staff (only Enrica Alteri was visible) but also 2 of 6 names for “PRAC
Rapporteurs /assessors.” We have not seen any explanation anywhere why we were only allowed to
see who 4 of the 6 rapporteurs /assessors were: Julie Williams, Qun-Ying Yue, Jean-Michel Dogne
and Ulla Wandei-Liminga. Elsewhere, e.g. in the 256-page internal report, only two co-rapporteurs
and one rapporteur are mentioned (4), and we therefore thought there were only these 3 people
and not 6.
When we asked the EMA why it had redacted names of some PRAC rapporteurs /assessors, we were
told: "However, the document has been redacted in accordance with Article 4(1)(b) of the
Regulation and the European Union legislation regarding the protection of personal data. All
protected personal data was redacted in order to avoid that the disclosure of the document would
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undermine the privacy and integrity of any individual. In particular, names of PRAC assessors and
EMA support staff have been redacted according to the Agency's policy on access to documents and
the ‘Output of the European Medicines Agency policy on access to documents related to medicinal
products for human and veterinary use’” (18). We appealed to the EMA on 10 June 2016 saying (31):
“We cannot understand why the EMA redacted some names but not others. Such selective redaction
of names inevitably raises suspicions, e.g. about whether the redacted persons have important
conflicts of interest in relation to the HPV vaccine manufacturers” and we asked for a document
where no names had been redacted. The EMA responded on 11 July (see below under item D8).
D8. We also showed an example of an absurd redaction, which came from the “PRAC co-rapporteur’s
referral updated assessment report” (25). It is clear to anyone familiar with this area that the word
left out must be “Denmark.” The example also illustrates that there was far more uncertainty and
disagreement than the EMA’s official report reveals. The Swedish co-rapporteur (SE means Sweden)
was obviously not happy with the approach taken and also criticises the observed versus expected
incidence comparison of possible harms of the vaccine rather heavily, just like we have done.
The EMA’s reply to us was totally unconvincing and it also demonstrated that the EMA no longer
respects the ombudsman’s ruling in our previous EMA case from 2010 (10). The EMA argued that all
redactions made in the documents are in accordance with the requirement of the regulations and in
line with the EMA's Policy and Rules. The EMA “has redacted all health data that could lead to the
identification of a natural person,” which includes date of birth, reporting country, patient
identification code, patient numbers, case report numbers, site numbers and “any other information
that may lead to the identification of a patient in the context of a patient narrative. However, the
information taken into consideration in the assessment reports which does not permit identifying
individual patients has not been redacted” (pp11-12).
The EMA redacted much more in its HPV documents than the ombudsman considered necessary in
2010 when he noted that the documents we requested did not identify patients by name but by
their identification and test centre numbers and that the only personal data are those identifying the
study authors and principal investigators (10). In 2011, the Nordic Cochrane Centre requested clinical
study reports on antidepressant drugs from the EMA, and some of these contained patient
narratives (brief summaries of deaths, serious adverse events, or other events of clinical importance)
or listings of adverse events in individual patients with details including the patient identifier (32).
The fact that the patient identifier was not redacted (in fact nothing was redacted) meant that it was
possible to compare information in the text of the reports with that in tables and narratives. This led
34

to the interesting discovery that four deaths were misreported by the company, in all cases
favouring the active drug (32). It was also demonstrated, for the first time, that antidepressants
double the incidence of aggression compared to placebo in children and adolescents (32), which can
help explain why antidepressants may drive healthy people into committing suicide or homicide
(16,33).
The AbbVie case shows that the EMA currently redacts a lot of information it should not have
redacted (see item B9). We believe there is a strong overriding public interest in not having essential
information redacted that can be important for patient safety. For example, we found important
inconsistencies within the clinical study reports with respect to the reporting of adverse effects
(32,34,35). The EMA’s current approach, which we believe is illegitimate, can make research such as
that on antidepressant drugs impossible.
The EMA provided a very long explanation when it disagreed with our view that "it is not possible to
identify individual people from a case number," referring to a number of regulations and rules (p12).
As noted above, all such documents are open to interpretation and the EMA seems to interpret
them in the most restrictive way possible. Even so, the EMA is highly inconsistent in its decisions
(10,15,20-22,32), and the minute risk of identifying a real person person needs to be weighed
against the risk that many patients are being harmed and die because vitally important research
about drug harms is being withheld by the EMA by all its unnecessary redactions.
The EMA noted that it redacts personal data, e.g. names, “of some EMA staff involved in pre- and
post-authorisation activities” to protect the privacy of individuals, “in particular concerning the
identity of EMA staff members that are part of the EMA secretariat and do not take part in the
elaboration of the scientific opinion of the EMA scientific committees” (p12). We cannot understand
why the EMA deletes names of people who are not involved with the scientific work and we doubt
there are legitimate reasons for it. People who work with public administration for the common
good should not hide who they are in an open and transparent society. On 11 July, the EMA
explained that, “In particular, the exception applicable is in accordance with Article 4.1. (b) of the
Regulation, whereby the Agency shall refuse access to a document where disclosure would
undermine the protection of privacy and the integrity of the individual, in particular in accordance
with EU legislation regarding the protection of personal data” (36). We fail to understand why a
person’s name can be regarded as “personal data” that needs protection because “disclosure would
undermine the protection of privacy and the integrity of the individual .” By personal data, we
understand, for example, a person’s previous diseases and admissions to hospital. We believe the
EMA’s interpretations of the rules are highly questionable.
The EMA wrote: “However, personal data relating to EMA staff with managerial and official functions
is not redacted and their names and contact details are published on the EMA website” (p13). Again,
we cannot see any rationale for this sharp distinction between public servants in different roles.
The EMA noted: “Moreover, the names of committee members involved in the evaluation of
medicinal products are considered releasable and the information is proactively published on the
EMA website. In accordance with Article 4(2) 1 st indent of Regulation (EC) No 1049/2001,
commercially confidential information should be redacted in order to avoid that the disclosure of the
document would undermine the protection of commercial interests of a natural or legal person,
including intellectual property. In this case, doses of vaccines distributed and number of cases per
35

country are considered confidential information regarding sales data. This is in line with the
‘HMA/EMA recommendations on transparency: Recommendations on the handling of requests for
access to periodic safety update reports’ 25 . While global sales in the EU are not considered
commercially confidential and are not redacted, sales by individual country could disclose sensitive
information concerning the company's commercial and business strategies and was considered
commercially confidential and redacted in accordance with Article 4(2) 1 st indent of the Regulation.
We would like to point out that, although mentioned in your letter, in this context country names
were not redacted” (p13).
It is not correct that country names were not redacted and we gave an example above where
“Denmark” was redacted. We have also observed that, in many countries, e.g. Denmark, detailed
sales statistics are freely available on the internet making it possible for everyone to see how much
of a given product that has been sold, in which regions and to which age groups, etc. It therefore
makes no sense that the EMA interprets Regulation 1049 so narrowly and considers such data
“commercially confidential information.” Regulation 1049 can be overruled if there is an overriding
public interest that is more important than to protect drug companies, which there surely is in this
case. Without access to sales data, it is not possible to perform meaningful research on the incidence
of serious harms possibly caused by the vaccines because no independent verification of
denominators (number of doses sold or number of people vaccinated) used for rate construction can
be carried out.
The EMA argued that, “In accordance with Article 4(3) 2nd paragraph of Regulation (EC) No
1049/2001, documents containing opinions for internal use as part of deliberations and preliminary
consultations within EMA shall be refused even after the decision has been taken if disclosure of the
document would seriously undermine the EMA's decision-making process. This is also reflected in
the EMA's Policy under the section ‘Protection of internal deliberations’. In this regard, EMA
redacted the names of the EU Member States that submitted comments to the assessment reports.
While the content of the comments themselves is not redacted, EMA does not disclose the identity
of the EU Member State which made the comment. The disclosure of this information would
undermine the collegial and confidential nature of the discussion and would deter the EU Member
States from having open and comprehensive discussion in future procedures” (p13).
We find this argumentation bizarre. With the same type of argument, one could postulate that
members of the European Parliament should all be anonymous and should all be wearing disguise
when they debate in Parliament in order not to deter them “from having open and comprehensive
discussion.” In a democracy, people are responsible for their actions and opinions and should be
held accountable for them. If people or public institutions have something to hide and hide it, it
doesn’t foster public confidence in the procedures or give them legitimacy, and it may open the door
to corruption.
Corruption is very common in healthcare, and it also occurs at drug agencies, which the many
scandals at the US Food and Drug Administration show (11). Corruption has also occurred in Europe,
e.g. in Italy (11). Duilio Poggiolini, general manager of the pharmaceutical department of the Italian
Ministry of Health, was arrested in 1993 due to a series of charges related to forgery and bribery
favouring the entry of useless drugs (37). The scandal involved the minister of health who arranged
for drug companies to pay bribes in order to get their drugs approved and sold at “suitable” prices
(38). The corruption network also involved academics who received shares of the bribes in return for
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expert advice in favour of the drugs, some of which were dangerous and sold at exorbitant prices. In
2008, the vice president of the Italian Drug Agency, Pasqualino Rossi, one of Italy’s most senior
representatives at the EMA, was arrested (39). Six drug company lobbyists were also arrested, and
the case concerned alleged falsification of clinical data in return for cash, revealed by wire tapping
and covert cameras. The prosecutor said the corruption had resulted in concealment of lifethreatening
harms of the drugs. The drug agency issued a statement that none of its employees
were under investigation, but when the Italian press named the senior officials arrested, the
statement was removed and a new one was being prepared. The fact that corruption occurs at drug
agencies is a very good reason for being open about everything, including who said what. Secrecy
makes it much more difficult to detect corruption.
The EMA noted that, “Regarding the mentioned publication identifier for an article in press that has
been redacted, this has been an error” (p13).
Uncertainties in the science that were left out of the official report
We wrote to the EMA that there was much genuine uncertainty about what the science tells us and
whether further research is needed, and that there was also a lot of disagreement in the EMA’s
working group that is not apparent in the official report. We gave some examples from “PRAC corapporteur’s
referral updated assessment report” from 28 October 2015 (25).
E1.The updated assessment report noted: “We agree with the limitations in the current data, but we
do find it important not to dismiss the issue at this point but to consider studies or other activities to
gain additional information in the future. Also we find that active communication and involvement of
all relevant stakeholders is key to address current and future public concerns and ensure the public
confidence in the national vaccination programs” (25, p9).
This didn’t happen. The EMA left no doubt in its official report that the vaccine is safe (2).
The EMA wrote to us: “It is confirmed that there are indeed two Co-Rapporteurs' assessment
reports, one from the Swedish Co-Rapporteur and one from the Belgian Co-Rapporteur and this is
stated in the reports. The document referenced extensively in the Cochrane letter is the Preliminary
assessment report by the Belgian Co-Rapporteur ... The PRAC (Co)-Rapporteur has reconsidered their
[sic] position following the interaction with the previously named stakeholders; this updated position
was reflected in the joint report ... The PRAC reached its scientific recommendation by consensus
following the plenary discussion ... The PRAC recommendation was endorsed by the Committee for
Medicinal Products for Human Use (CHMP) who issued its Opinion following a review and a plenary
discussion. The two Committees concluded that there was no evidence of a causal link between HPV
vaccination and the two syndromes CRPS and POTS” (pp13-14).
Much of the information obtained from the EMA is confusing. We thought the updated assessment
report reflected the views of both co-rapporteurs because the report said “we” in several places. The
EMA now tells us that it was the view of one of them only but nonetheless wrote, “The PRAC (Co)-
Rapporteur has reconsidered their [sic] position.”
We consider the EMA’s explanation unsatisfactory. When there is genuine uncertainty in science
about rare, but serious harms possibly caused by a preventive medical intervention in children, it is
37

not appropriate to use consensus methods and then convey to the public the impression that
“everybody agrees that there is nothing to worry about.” The EMA has repeatedly stated that the
benefits of the vaccine outweigh its harms. But that is not what the public is concerned about. The
issue is whether or not some people are being seriously harmed by the vaccine. Although the EMA
cannot rule out this possibility, it seems to us that the agency has nonetheless tried to do exactly this
in its communications to the public. There is enough evidence to substantiate a suspicion of serious
harms, which is what motivated the DHMA to call for an investigation. The EMA’s unwarranted
certainty has been met with disbelief and has resulted in a dramatic decline in vaccine uptake, the
exact opposite of what the EMA wanted. In Fyn in Denmark, the uptake of the vaccine decreased
from 74% to 31% in just one year (40).
E2, 3 and 5. As the EMA replied to items 2, 3 and 5 together, we have inserted these replies, and our
comments on them, after all three items.
E2. The updated assessment report noted: “In the search for cases coded as POTS in the database
the MAH make a further selection by case definition criteria that appears too limiting. Only cases
that are medically confirmed have been included, which is reasonable for a diagnosis such as POTS
that cannot be expected to be verified by a consumer. 83 reports are identified as medically
confirmed but out of these almost half (40 cases) are then dismissed for not meeting the case
definition for POTS. It appears that they have been dismissed mainly due to lack of information in
the reports. This does not appear to be in accordance with good practice, since spontaneous reports
cannot be expected to describe all details for a diagnosis given to a patient. As also pointed out in
the rapporteurs AR [we assume this means assessment report] p.22, we agree that when a diagnosis
is reported and verified by a HCP [we assume this means health care practitioner], this description
should be accepted and used in the further work e.g. observed versus expected ratios” (25, p9).
We wrote to the EMA that the “co-rapporteurs are highly critical of the approach of the MAHs and
find that ‘when a diagnosis is reported and verified by a HCP, this description should be accepted
and used in the further work e.g. observed versus expected ratios.’” We also said that it is
noteworthy that the co-rapporteurs agreed with Brinth (see item C7 above) and that “this support
for her arguments did not make it to the EMA’s official report (2). We believe that an assessment
provided by a clinical expert who sees the patient is likely to be far more reliable than that
performed by a company employee with a conflict of interest looking at paperwork.”
E3. The updated assessment report noted: “The main conclusion in the Danish report is not, as
described in the assessment, to change focus to CFS. Rather the review highlights the necessity to
evaluate combinations of symptoms rather than only performing separate evaluations of individual
diagnoses. It shows that although the number of POTS cases is very high in Denmark, compared to
the rest of the world, the symptom pattern seen in the Danish dataset is similar to reports submitted
from other countries. Even though it cannot be shown for certain at this point, it is likely based on
these data, that patients with the same symptomatology would receive different diagnoses in
different member states e.g. POTS in DK and CFS/ME in others. This consideration is important for
the discussion of consistency regarding the POTS signal, where it is stated that the finding of the
majority of POTS cases in Denmark does not support a causal relationship. We do not agree with this
conclusion based on the data” (25, p9).
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The EMA’s explanation to us that only one of the two co-rapporteurs was critical is misleading. Why
say “We do not agree with this conclusion based on the data,” if it is only one of them who
disagrees? The co-rapporteurs (in plural, as we believe it is both of them) are highly critical of the
EMA’s draft report and yet again, they agree with Brinth, but this strong support for her arguments
did not make it to the EMA’s official report (2). The EMA told us that it was only the Belgian corapporteur
that was critical, but we explained above (item D7) that also the Swedish co-rapporteur
was critical of the approach taken and criticised the observed versus expected incidence comparison
of possible harms of the vaccine rather heavily.
E5. The updated assessment report noted: “We support DHMA comment that due to differential
clinical practice across countries, similar suspected ADRs [adverse drug reactions] to HPV vaccine are
receiving different diagnoses (or indeed no clear diagnosis), which in turn may be potentially
'diluting' a safety signal” (25, p11).
The co-rapporteurs’ support for the concerns of the DHMA that asked the EMA in July 2015 to assess
possible serious harms of the vaccine were not included in the EMA’s official report (2).
There are additional examples in the EMA’s confidential, internal report (4) of important
disagreements and observations that are not revealed in the official report (2). In several of these
cases, the rapporteur disagrees with the two co-rapporteurs, but it is only the rapporteur’s opinion
that is presented in the official report.
The EMA wrote to us in relation to items 2, 3 and 5: “The comments quoted here are comments
made by one Member State, not by the (Co)Rapporteurs of the procedure. The comments were
considered and discussed by the (Co)-Rapporteurs in their Updated assessment report. The final
PRAC assessment report was adopted by consensus; therefore the Member State that raised the
original comment considered that it was sufficiently addressed” (p14).
Again, we can see no legitimate reason for the EMA to hide which Member State it is. We find it
highly likely that the Member State is Denmark, since it was Denmark that raised the issue about
vaccine safety, and since the Danish drug agency was critical towards the way the EMA assessed this
risk. Politically, it is very common that a critical Member State expresses satisfaction if it is in a clear
minority in a consensus discussion, but this whole affair is not about politics, it is about science.
There is considerable public interest in knowing whether the disagreeing Member State was
Denmark.
The EMA also wrote to us: “There is no explicit agreement in the assessment reports (draft or final)
from the (Co)-Rapporteurs, with any of Dr Brinth's statements or with the conclusion of her
publications, apart from the following: ‘Taken together; it is agreed with the authors that this case
series does not provide sufficient data to establish a reasonable possibility of a causal relation
between the HPV vaccine and POTS.’” (p14)
The EMA misrepresents seriously the facts. We have explained above that the Belgian and the
Swedish co-rapporteur agreed with Brinth on many important issues related to HPV vaccine safety!
39

E4. The updated assessment report noted: “However, as the potential involvement of Cervarix in the
occurrence of CRPS cannot be completely ruled out at this stage, the co-rapporteur recommends
that this risk should continue to be investigated” (25, p7).
“We agree with the conclusion from the rapporteurs and also state in the Danish report, that the
data from spontaneous reports cannot be used to provide evidence for a causal relationship
between symptoms and vaccination. However in view of the methodological limitations of the data
available and the fact that the observed cases did exceed the expected cases, especially in Japan and
Denmark, the conclusions should be cautious and the signal cannot be dismissed either based on the
current evidence. We recommend that the vaccine SAG and expert meeting include a discussion of
the need and possibilities to design appropriate PASS studies to explore POTS further. Similar
question as Q3 regarding CRPS” (25, p10).
It was not specified in the assessment report who “we” are but “we” are highly likely the Danish
Health and Medicines Authorities (DHMA). Again, it is not clear whether one or both co-rapporteurs
agree with Brinth and the Danish authorities that more research is needed. The Danish authorities
“agree with the conclusion from the rapporteurs,” i.e. both of them (25, p10). But this support for
Brinth’s arguments was not included in the EMA’s official report (2). In the EMA’s confidential,
internal report, the rapporteur dismissed the proposals by the Belgian co-rapporteur: “The
Rapporteur agrees with most conclusions af the Co-Rapporteur (BE) for Cervarix, with the exception
of the recommendations in relation to further evaluation of CRPS and POTS” (4, p5).
The EMA wrote to us: “In the first and fourth paragraphs, the statements of the Belgian Co-
Rapporteur are presented ... The final PRAC assessment report was commented and endorsed by the
three (Co)-Rapporteurs and ultimately by the whole PRAC, and subsequently by the CHMP. The
individual (Co)-Rapporteurs' assessment reports represent the view of individual teams at
intermediate phases of the procedure. They, thus, constitute interim reports, which undergo several
modifications during the procedure, hence they are not published ... Specifically concerning the
criticism on the preliminary divergent view of the Belgian (Co)-Rapporteur which was subsequently
changed and reflected differently in the joint report, it should be clarified that in their preliminary
assessment, the Belgian (Co)-Rapporteur considered that the evidence did not permit either to
conclude or to exclude an association with CRPS and, based on this preliminary view, proposed a
PASS to gain further evidence on the potential association. The SAG experts considered a PASS
although feasible to be conducted, was unlikely to produce robust results given the difficulties in
identifying the cases and the potential biases. Taking into consideration this element and the overall
SAG discussion, as well as their updated view on the causality assessment, the Belgian Co-
Rapporteur reconsidered the need for a study to be requested from the manufacturers” (pp 14-15).
These statements are confusing. The EMA speaks about “three (Co)-Rapporteurs” although there
were only two. And we are told, for the first time, that the “individual (Co)-Rapporteurs' assessment
reports represent the view of individual teams.” This may explain why the dissenting co-rapporteur
says “we.” The two co-rapporteurs were likely the most important of all the people that participated
in the EMA’s processes, as they are those “who take the lead in the scientific assessment and who
have the task of thoroughly assessing the data and draft their recommendations which is [sic] then
shared with all PRAC members” (p4 in the EMA’s letter to us).
40

E6. We found this in the EMA’s internal document: “Rapporteur's comments on the Brinth et al case
series: ... In summary, the case series reported by Brinth et al represents a highly selected sample of
patients, apparently chosen to fit a pre-specified hypothesis of vaccine-induced injury” (4, pp225-6 in
pdf, or 46-47/77 in the subdocument). We wrote to the EMA that this defamatory remark about
Brinth’s research is exactly the same as in the EMA’s official report: “apparently chosen to fit a prespecified
hypothesis of vaccine-induced injury” (2, p24).
The EMA replied: “The views expressed by the (Co)-Rapporteurs and by the PRAC with regard to the
Brinth data represent a critical assessment of the data and the type of study from a purely scientific
perspective. And in no way it is intended to undermine - or endorse - the credibility of any expert.
Such views may or may not be shared by all parties, but nevertheless they remain the views of the
PRAC” (p15).
We believe that it is totally unacceptable that the EMA published (2) a remark that lacks any
foundation and furthermore failed to mention that Brinth and her colleagues had themselves
pointed out the well-known limitations of their research design. We also reject the EMA’s argument
that this should have anything to do with a critical assessment of the data and type of study from a
“purely scientific perspective.” If the EMA didn’t intend to undermine Brinth’s credibility, then why
did the agency publish a sentence that could undermine a person’s scientific reputation (4)?
E7. We wrote to the EMA that Dr Luc Kiebooms and Dr Andre Devos motivated in their submitted
statements why a safety study was needed (4, pp171-4 in the pdf, or 59-62/67 in the subdocument):
“The Vioxx scandal 2 and Diane-35-problems have shown how weak [safety] reporting is. In both
cases there has been reporting for years, but this was done with the same methodology as suggested
here. So the insight into the actual extent and severity of the phenomenon was slowed down
tremendously. In both cases afterwards it turned out, that the makers of the medicine knew of the
adverse reactions, before the medication was brought into circulation. For HPV now, the same
seems to occur. We are at the stage of a reporting of a particularly large number of cases for a
vaccination, for which a zero tolerance regarding the side effects should prevail 3 . Until now all the
literature is exclusively under the direct supervision of the industry, probably even all information
comes from the industry. There are no independent studies, despite the fact that these were raised
on several levels.”
“Initially, the vaccine was compared with a placebo group being vaccinated with physiological serum,
whereby the number of adverse reactions was much higher and much more serious than in the
control group. After comparing 320 patients in the saline placebo group a quick move was made to
an aluminium-containing placebo, in order to be able to only evaluate the effects of the active
substance. However, this distorted the comparison, because no one voluntarily wants to be
vaccinated with toxic aluminium, as this is not really necessary, when inoculation with a harmless
saline solution can be done. The differences between Gardasil and the saline placebo group were,
however, already noticeable 15 .... the difference between the vaccine and the saline placebo is
concealed in all publications, as the table below clearly shows. For serious adverse reactions one
suddenly takes the saline and aluminium group together, perhaps to cover up the major differences
between these two groups.”
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We wrote to the EMA that these two doctors questioned seriously the prevailing assumption,
apparently also at the EMA, that the vaccine is so important for public health that it is justified not to
communicate to the public that:
1) There are uncertainties related to vaccine safety;
2) Drug companies cannot be trusted; and
3) It is wrong to lump together results obtained with a genuine placebo with those obtained with a
potentially neurotoxic placebo.
We agreed with the two doctors when they suggested that this lumping may represent a cover up
and we also found that the EMA should have informed the public about this unacceptable lumping of
a true placebo with an active placebo instead of keeping it secret. We noted that we found this
totally unacceptable and contrary to good scientific practice to such a degree that we considered it
outright scientific misconduct committed by the EMA.
The EMA replied to us that this was “the view of members of public who submitted spontaneous
information which were included in the Belgian Co-Rapporteur's assessment report.” The EMA
furthermore explained: “As already clarified, it is a matter of balance between benefits and risks and
it is acknowledged that the evaluation needed to conclude on this balance can be extremely
complex. Moreover presenting in a short report how the whole of the available evidence has been
assessed and weighed to reach those conclusions may also be complex. EMA is striving to always
improve the quality and clarity of its assessment reports to ensure maximum transparency, so that
the European public can see how decisions were made. It also aims to fairly represent the open and
thorough way in which European experts work at EMA” (p15).
It is not correct that the EMA ensures “maximum transparency, so that the European public can see
how decisions were made.” It is clear from our complaint to the ombudsman that it is hard detective
work to find out what went on in the HPV case and why, and we have spent months on this. As we
have explained in detail above, not even the EMA’s 254-page internal report comes any way near
“maximum transparency.” We found out who the members of the PRAC and SAG committees were
via other sources. The is more akin police work than scientific work. The ombudsman needs to
ensure that secret meetings at the EMA under a gagging clause will not be possible in future.
The MAHs presented their position during the open session at the SAG meeting. We believe that this
should not be allowed. The companies can send what they have; they should not present at
meetings because of their huge conflicts of interest and the psychology that is at play: Nice people
tend to win arguments, and people may not ask critical questions in order not to “offend” the invited
presenter.
We did not know who Dr Luc Kiebooms and Dr Andre Devos were but were told by the EMA (for the
first time, which is not “maximum transparency”) that they were “members of public who submitted
spontaneous information which were included in the Belgian Co-Rapporteur's assessment report.”
This is very important information. The contributions of Kiebooms and Devos are the only ones in the
whole 254-page report that alert people to the well-documented fact that drug companies cannot
and should not be asked to audit their own work (11,16). Nonetheless, the EMA trusted almost
blindly the two drug companies in the HPV case, which we believe is not a legitimate approach. The
fact that the Belgian co-rapporteur included this information, which is highly critical of the drug
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companies, in his report makes it even more unacceptable that this rapporteur was overruled in the
“consensus” process, and that not a trace of his criticism was left in the EMA’s official report.
We believe that the EMA gets its task wrong when it argues that, “As already clarified, it is a matter
of balance between benefits and risks and it is acknowledged that the evaluation needed to
conclude on this balance can be extremely complex.”
Firstly, the semantics are wrong. A benefit is a given, not something hypothetical, whereas a risk is
hypothetical, as it may or may not happen. This is to turn things on their head. A drug, including a
vaccine, ALWAYS causes harms, whereas we cannot know whether it has any benefits. Therefore, we
should rather be speaking about the balance between potential benefits and certain harms, but we
could also simply refer to the balance between benefits and harms (41).
Secondly, the balance between benefits and harms is highly subjective, and different people will
reach different conclusions based on the same data. For example, although it is officially
recommended to take influenza vaccination, many specialists in infectious diseases have declared
publicly that they won’t take them. We do not believe that it is the primary task of a drug agency to
come up with subjective statements or to recommend interventions. The EMA’s primary task is to
ensure that the public gets as accurate and independent information as possible about the benefits
and harms of the products it approves, so that they may decide for themselves whether or not they
want to use the products. The EMA has not done this for the HPV vaccines.
Conflicts of interest
According to laws of public administration in several European countries, people should never be in a
position where they are being asked to evaluate themselves or where they have a personal or
financial interest in the outcome. For example, Danish law states (our translation):
“Anyone who works in the public administration is disqualified in relation to a particular case if he or
she has a special personal or financial interest in the outcome ... The person who is disqualified in
relation to a case does not make decisions, participate in decision making or otherwise assist in the
consideration of the case.”
F1. The EMA stated in its internal report that the EMA asked the MAHs to provide “a cumulative
review of available data from clinical trials, post-marketing and literature in order to evaluate the
cases of CRPS and POTS with their product ... an analysis of the observed number of post-marketing
cases of CRPS and POTS in association with their HPV vaccine in comparison to those expected in the
target population, stratified by region, if available ... a critical appraisal of the strength of evidence
for a causal association with HPV vaccine for CRPS and POTS ... The responses submitted by the
different companies were assessed by the PRAC's Rapporteur (attachment 1) and Co-Rapporteurs
(attachments 2 and 3) for this procedure. Before adopting a recommendation, the PRAC decided to
convene the Scientific advisory group (SAG) on Vaccines and additional experts on vaccine safety,
neurology and cardiology to provide an independent advice and responses to the questions below”
(4, p5).
We noted in our complaint to the EMA that it is clear from its confidential document (4) that the
EMA relied heavily on the companies to come up with honest answers to highly complicated
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questions, and that the work of the EMA’s various assigned experts was not to verify what the
companies had done, but merely to summarise and discuss it. We found that this procedure provides
poor protection of public health, particularly considering that there are so many egregious examples
that companies have cheated by omitting major harms - including deaths - in their reports to the
authorities (11,16). We found it unacceptable that the EMA did not check the veracity of the MAHs’
work.
The EMA replied that, “The EMA has thoroughly and critically reviewed the data and analyses
presented by the MAHs, and all other information available. This means an in-depth assessment
which is performed by multiple experts who can ask for any clarification or additional information
that is required. Moreover, EMA also relied on various confirmatory sources of information such as
published literature and data from pharmacovigilance databases” (p15).
The EMA’s reply is seriously misleading. Nowhere in the 254-page report is there any information
that indicates that the data and analyses delivered by the drug companies had been “thoroughly and
critically reviewed,” the raw data re-analysed or even just checked. For example, as we stated under
item C8, the EMA uncritically reproduced the incidence rates of CRPS and POTS constructed by the
manufacturers. Furthermore, nowhere in the report is there any mentioning that any expert asked
the companies for clarification of vitally important issues. If this had been the case, we would have
expected to see a note about it, e.g. saying that one or more companies did additional analyses and
describing what these analyses showed. We find it unacceptable that the EMA simply believed what
the companies told them. The police don’t believe what suspects tell them; they check it. And since
it has been documented that the business model of drug companies involves deception (11),
information that comes from them should always be “thoroughly and critically reviewed” and
checked, just as the police would when dealing with known suspects.
The EMA also stated that, “Companies have the legal obligation to provide all available data they
have in their possession to the regulatory authorities and there are mechanisms in place to ensure
that this is abided by” (p15).
As we have explained above, a theoretical mechanism is not worth much if it is not being used when
it is relevant to use it. It has been amply documented that companies often omit important data or
seriously misrepresent them - also when they involve suicides and other deaths - in their submissions
to regulatory authorities and that the authorities let them get away with it even when they are
aware that they have been cheated by the same companies earlier in relation to the very same
issues (11,16). Even when drug agencies find out that drug companies have been less than candid
with lethal consequences, they don’t require the companies to tell the public about the many deaths
they omitted from their published clinical trial reports (11,16). In any case, we have provided
mathematical proof that the EMA did not check what they already had available and did not ask for
data that were not in their holdings.
The Nordic Cochrane Centre has worked with protocols and clinical study reports for antidepressant
drugs submitted to the EMA for obtaining marketing authorisation, and by comparing the Index with
what was obtained from the EMA, it became clear that whole subdocuments and appendices were
missing (34,35). Other Cochrane researchers found that 15 of 16 study reports on oseltamivir for
influenza received from the EMA lacked the appendices containing listings of effectiveness and
adverse events, and there were no case report forms for important adverse events for any of the
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trials (42). This suggests that the EMA does not check that they have received all relevant
documentation when the agency decides to approve a new drug. This practice is also unacceptable.
We are aware that, under Directive 2001/83/EC and ICH E3, appendices do not necessarily have to
be submitted to the EMA as part of the regulatory submission for marketing authorisation, but the
sponsor must make these available to the EMA on request (35). The “Note for guidance on the
inclusion of appendices to clinical study reports in marketing authorisation applications” lists the
appendices required to be submitted to the EMA with each clinical study report. These appendices
include the protocol and amendments to the protocol. When the EMA doesn’t possess all
documents, relevant independent research may not be possible, and the public might get
misinformed by our drug regulators. In our experience, drug agencies are unwilling to contact the
MAHs and ask for the missing documents. When the Nordic Cochrane Centre, for example, wanted
to look at suicidality events in the extension phase of trials of the antidepressant drug, duloxetine,
for urinary incontinence, the researchers found out that the EMA did not possess these important
documents (43). The US drug agency (FDA) seemed to have them, as the agency stated that a higher
than expected rate of suicide attempts was observed in the open label extensions of the controlled
trials (43). Similarly, the EMA does not hold the Case Report Forms for serious adverse events
reported in the HPV vaccines trials.
F2. At a hearing about HPV vaccine safety in the Danish Parliament on 17 December 2015, which was
video recorded (44), Enrica Alteri from the EMA told the audience that the EMA’s Scientific Advisory
Group consisted of members who were independent. However, she also said that they had declared
their conflicts of interest (her remarks on this point were not translated by the simultaneous
translation). As we explain below, some of these experts were not independent. Alteri told the
audience that the HPV vaccine can prevent most, if not all, deaths from cervical cancer. She walked
out immediately after her presentation with no excuse and did not take questions or participate in
the panel discussion. This was perceived by some in the audience, which included Danish politicians,
relatives of girls with severe symptoms, the media and scientists, as being blatantly arrogant and
counterproductive in terms of building trust in the vaccines and in the EMA.
We wrote to the EMA that we found it totally unprofessional and misleading to the extreme to
suggest that the HPV vaccine can prevent all deaths from cervical cancer. Such a claim would not
have been tolerated by the EMA if it had come from one of the manufacturers. The EMA states itself
in its publicly available report that the different vaccines don’t protect against infection from all HPV
strains, only from 70%, 80% and 90% of the strains, respectively, and that the vaccines are not 100%
effective against the targeted strains (2). We also found it inappropriate to use experts with financial
ties to the manufacturers, as it is always possible to find experts without such conflicts.
The EMA provided a lengthy response to us on this important issue (pp15-17):
“EMA takes due care to ensure that its scientific committee members and experts, including SAG
members and experts, do not have any financial or other interests that could affect their impartiality
... Each expert has to make a declaration of interests (annually or earlier if their interest change)
which EMA's secretariat scrutinises and assigns an interest level based on whether the expert has
any interests in pharmaceutical industry, and whether these are direct or indirect.
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After assigning an interest level, the level of participation in the EMA's activities is determined by 3
factors: the nature of the declared interest, the timeframe during which such interest occurred, as
well as the type of activity that the expert will be undertaking.
The overall principles of the policy can be summarised as follows:
• Current direct interests in pharmaceutical industry, i.e. current employment, current consultancy,
current strategic advisory role and current financial interests are incompatible with involvement in
any EMA activity. There are however two exceptions:
i) current consultancy for an individual medicinal product and current strategic advisory role
for an individual medicinal product are allowed for SAG and ad hoc expert group Chairs,
members and experts, but restrictions on involvement apply (i.e. the expert cannot
participate in any activity regarding the declared product) and
ii) current consultancy, current strategic advisory role and current financial interests are
allowed for an expert witness who's involvement is limited to testifying and giving specialist
advice on a specific issue by providing information and replying to any questions only, but
with no involvement in the final discussion or deliberations on the issue.
• Past direct interests, e.g. past employment, past consultancy, past strategic advisory role and past
financial interests, as well as current or past indirect interests, e.g. principal investigator,
investigator, grant/other funding to organisation/institution and close family member interests are
allowed, but may result in restrictions in involvement depending on their nature, their timeframe of
occurrence and the type of activity.
In the interest of transparency, the declarations of interests and curriculum vitae of experts are
published on the EMA's website and the outcome of their evaluation and the applicable restrictions
are included in meetings' minutes.
We would like to assure you that the policy was correctly applied to the participants of the SAG
meeting on HPV vaccines which took place on 21 October 2015. The declarations of interests were
evaluated and restrictions on experts' involvement were applied based on the principles described
above.
In line with the policy, experts who had declared current direct interests in a pharmaceutical
company or for a particular medicinal product were allowed to participate in the SAG meeting:
• with restrictions resulting in either exclusion from the final deliberations or involvement as 'expert
witness' (this role was limited to testifying and giving specialist advice on this specific issue by
providing information and replying to any questions only), or
• with no restrictions (if the interests declared did not present a potential conflict of interest with
respect to the specific topic discussed at this SAG meeting).
Experts who declared past direct interests and indirect interests were allowed to participate in the
meeting with or without restrictions. Where restrictions applied (if the interests declared presented
46

a potential conflict of interest with respect to the specific topic discussed at this SAG meeting), those
experts were not allowed to participate in the final discussion and decision.
We would also like to highlight to you that the format of participation for Enrica Alteri at the hearing
on HPV vaccine safety at the Danish Parliament on 17 December 2015 was agreed ahead of the
hearing with the organisers. We are surprised by your comments on Enrica Alteri's presentation
since the feedback provided to EMA was that her presentation was very well-received at the
hearing.”
We find that all these rules and exceptions are so complicated and vague that it is impossible to
apply them consistently, not only from case to case but even within the same case. The
interpretation of the rules will also depend on who the chair is, and since chairs are allowed to have
financial conflicts of interest in relation to drug companies, one would expect such people to be
pretty lenient towards others with such conflicts. The whole setup is confusing and decisions are
bound to be arbitrary and person-dependent. We consider this garbled situation as undermining the
EMA’s legitimacy. No one can remember all the detailed instructions when making judgments.
Some of the EMA’s statements are wrong, e.g. “EMA takes due care to ensure that its scientific
committee members and experts, including SAG members and experts, do not have any financial or
other interests that could affect their impartiality.” The EMA doesn’t do this, and according to the
information we have, and the EMA’s own statements quoted above, some SAG members and
experts DID have such conflicts (see below). Enrica Alteri from the EMA therefore misled the
audience in the Danish Parliament when she said that the EMA’s Scientific Advisory Group consisted
of members who were independent.
We find it unacceptable that “current consultancy for an individual medicinal product and current
strategic advisory role for an individual medicinal product are allowed for SAG and ad hoc expert
group Chairs, members and experts” and we find it naive and unrealistic that the involvement of
expert witnesses with such conflicts” is limited to testifying and giving specialist advice on a specific
issue by providing information and replying to any questions only.” We also find it unacceptable that,
“In line with the policy, experts who had declared current direct interests in a pharmaceutical
company or for a particular medicinal product were allowed to participate in the SAG meeting.” It
seems to us that the EMA knows very little about group dynamics. Abundant psychological research
has shown that such precautions just cannot work as intended. The impact of all this on the EMA’s
credibility would be reduced if all limitations for all participants, with reasons, were made publicly
available.
According to Danish law, people who are disqualified in relation to a case does not make decisions,
participate in decision making or otherwise assist in the consideration of the case. The EMA needs to
adopt a similar approach. Conflicted people should not have anything to do with the work at the
EMA and should not be allowed to sit in committees, and if advice from them is needed, it can be
obtained in writing. Everyone can understand and remember this simple and transparent rule, which
is sensible, in contrast to the hopeless and garbled rules the EMA currently uses.
The EMA wrote to us that, “In the interest of transparency, the declarations of interests and
curriculum vitae of experts are published on the EMA's website and the outcome of their evaluation
and the applicable restrictions are included in meetings' minutes” and “We would like to assure you
47

that the policy was correctly applied to the participants of the SAG meeting on HPV vaccines which
took place on 21 October 2015.”
We believe it is impossible to ensure that a policy so complicated and vague “was correctly applied”
as no two persons would be able to apply such intricate rules in the same way throughout an EMA
process. Furthermore, the EMA was the judge for stating that the policy was correctly applied, which
represents a conflict of interest in itself. As noted above, we asked the EMA to provide us with the
names of the experts the EMA had used (18) and we also received minutes from the SAG meeting on
HPV vaccines on 21 October 2015 (24). Four people were not allowed to take part in the final
conclusions of the meeting because of their declared conflicts of interest. As the minutes from the
meeting did not specify what these interests were, we consulted the EMA’s website. Martin
Ballegaard was investigator on a study by Novartis in infants with type 1 spinal muscular atrophy.
Rolf Karlsten had multiple conflicts of interest in relation to drug companies and owned shares in a
company. Jesper Mehlsen was involved with a trial of an HPV vaccine from Merck, Sharp & Dohme.
Frank Huygen had been on the Advisory Board of Grünenthal till 2015 and of GlaxoSmithKline in
relation to its HPV vaccine till 2013.
There were no restrictions for the chair of the meeting, Andrew Pollard, although he had declared
several conflicts of interest in relation to the HPV vaccine manufacturers GlaxoSmithKline and Sanofi
Pasteur MSD until 2014 and 2013, respectively. In an article dated 24 September 2015 (while the
process at the EMA was ongoing and one month before the SAG meeting), which described a 12-year
old girl that had been diagnosed with chronic fatigue syndrome after having been vaccinated,
Pollard, the “chairman of the government’s Joint Committee on Vaccination and Immunisation
(JCVI),” was quoted as saying (45): “We have no evidence of a safety signal with the vaccine. But
what we do have is very clear evidence that this year 900 women, who have not received the
vaccine, will die of cervical cancer, and the vaccine has the potential to prevent such deaths in future
generations. So the place of this vaccine in defending women’s health is probably the most
important thing we have ever done.”
We expressed our consternation over all this to the EMA on 10 June 2016 (31) and appealed its
decision to redact the names of some of the co-rapporteurs and the names of most of the EMA’s
own staff. We noted that Pollard, who was a member of the expert group of the British government
responsible for the decision to include HPV vaccination in the childhood vaccination program in the
UK, seemed to have participated in the meeting with a predetermined opinion on the issue of
POTS/CRPS prior to the formal review of the data, and that, in a court of law, such evidence of
partiality prior to a trial would be grounds for exclusion from the jury. We asked the EMA to inform
us of its justification for offering the chair of the SAG, Andrew Pollard, privileges that were denied
others with similar or fewer conflicts of interest than the chair.
The EMA replied on 11 July (36). The EMA had redacted the identity of the PRAC Assessors, “who are
officials of the competent authorities of the EU Member States and are neither PRAC Members nor
EMA experts nor EMA staff,” in accordance with Article 4(5) of the Regulation and an “Output Table"
that was discussed and adopted by the EMA Management Board which includes representatives
from the EU Member States. However, following our appeal to the EMA, the “EMA consulted
exceptionally, taking into account this specific situation, the relevant EU Member States regarding
the release of the identity of their assessors notwithstanding the provisions of the Output Table. As a
48

esult, the Agency is now in a position to release the PRAC Assessors' names. Furthermore, the
Agency will consider amending the provisions of the Output Table for future instances.”
The names of the three PRAC assessors were Rolf Gedeborg, Phil Bryan and Suzie Seabroke.
According to the EMA’s website, they did not have conflicts of interest.
The EMA did not respond to our pertinent questions related to Pollard other than providing a
nonsense reply, considering the substance of our observations:
“Finally, with regard to your claim of a potential conflict of interest of the SAG's chair, please note
that the European Medicines Agency takes due care to ensure that its scientific committee members
and experts, including SAG members and experts, do not have any financial or other interests that
could affect their impartiality.” After this came some general statements about the EMA’s
procedures and “We would like to assure you that the policy was correctly applied to the
participants of the SAG meeting on HPV vaccines which took place on 21 October 2015.”
This demonstrates that the EMA’s policy was NOT correctly applied. It is pointless to exclude a
person from parts of the meeting who is investigator on a study by Novartis in infants with type 1
spinal muscular atrophy, which has nothing to do with the HPV vaccine, while allowing the chair of
the meeting to attend the whole meeting although he had recent conflicts of interest in relation to
the HPV vaccine manufacturers, and who in the press had praised highly the vaccines one month
before the crucial SAG meeting. Pollard spoke about the many lives it saved and said there was no
evidence of safety problems. The statement about the lack of harms was clearly inappropriate to
make for a chairman of an EMA committee in the middle of an ongoing process to assess whether or
not there is a safety signal. Furthermore, we found out that Enrica Alteri from the EMA, who had no
restrictions on her participation, nonetheless had conflicts of interest declared on the EMA’s
website. She was employed by Merck-Serono till June 2012 and her husband has a consulting
contract with Merck-Serono for 2016.
There were other reasons why the EMA’s policy was not correctly applied. As we stated under item
B7 above, we could not find any conflicts of interest declarations for two core members of the SAG
on the EMA’s website when we checked it in May 2016.
We hope the ombudsman will ask the EMA to respect the rules in future and also ensure that neither
chairmen nor other members of EMA committees have current or recent conflicts of interest.
The EMA wrote to us that the feedback provided to the agency from the meeting in the Danish
Parliament was that Enrica Alteri’s presentation was very well-received, but did not specify who
provided the feedback. If it was Enrica Alteri herself it would not count much, and it is difficult to
know how it was received when no questions or comments were allowed. One of us spoke with
several people after Alteri’s presentation, including one who had participated in one of the EMA’s
HPV vaccine committees and they were all very negative towards Alteri’s presentation, which was
perceived as arrogant and glossing over all the problems and disagreements that had been apparent
at the committee meetings.
F3. In our complaint to the EMA, we wrote that we believed that the EMA’s rapporteur Julie Williams
had conflicts of interest she had not declared on the EMA’s homepage. We apologize for this
49

mistake, which stems from the limited information that was available to us. In the material from the
EMA that we had acquired, we could not see where this person worked and therefore looked the
name up on the Internet. Unfortunately, we found the wrong person, another Professor Julie
Williams. Therefore, what we wrote about Professor Julie Williams in our complaint to the EMA
should be disregarded, apart from the sentence where we stated that she had declared no conflicts
of interest on the EMA’s homepage.
F4. We wrote in our complaint to the EMA that the EMA’s executive director, Guido Rasi, declared
on 20 July 2015 that he had no conflicts of interest (46). On a form called “EMA Public Declaration of
Interests,” he replied “none” to all four questions, also to question 4, which is: “Other interests or
facts whether or not related to the pharmaceutical industry 4 which you consider should be made
known to the Agency and the public, including matter relating to members of your household 5 .”
We also wrote: “However a Guido Rasi, which we assume is the same person, holds a number of
patents, some of which were filed or approved in 2012 or 2013, and where the applicant was a drug
company (Applicant: SciClone Pharmaceuticals, Inc.; Inventors: Guido Rasi, Enrico Garaci, Francesco
Bistoni, Luigina Romani, Paolo Di Francesco) ... As they go back less than five years, we believe Rasi
should have declared them, according to the EMA’s regulations concerning the handling of declared
interests of its employees“ (47,48).
Finally, we wrote: “The EMA’s director, Guido Rasi, has brought in a number of people from the drug
company Sigma Tau that include Stefano Marino, his head of legal affairs. Rasi has worked with this
company for many years and apparently owns several patents together with the company” (47).
This issue resulted in a long correspondence, which we believe has considerable public interest. The
correspondence included letters from Guido Rasi’s law firm marked “Private and confidential.” As
there is nothing private in them and we have not signed a confidentiality agreement with this law
firm or with Guido Rasi, and as we believe there is an overriding public interest in making our
correspondence publicly available that trumps any commercially confidential information we might
have overlooked, we have decided to include the entire correspondence in the Appendix to this
complaint to the ombudsman.
The first letter we received was written by the EMA’s Deputy Executive Director, Noël Wathion, 17
June 2016 (see appendix). Wathion wrote:
“EMA would like to refute your unsubstantiated allegations in the strongest possible terms ...
Amongst other things, EMA staff members are required to declare in their declaration of interests
(DoI) any ownership of a patent held for a period of 5 years prior to the start of employment with
the Agency ... An inventor ... is not necessarily the owner of the patent, e.g. the ownership rights
may be vested originally upon, or subsequently assigned to, a subject other than the inventor/s. Only
the owner of a patent can enjoy economic rights with regard to that particular invention. Therefore,
neither the applicable rules, nor considerations of common sense oblige EMA staff to declare in their
DoI any patents for which they are the inventor/s, but not the owner/s, unless the inventor is
entitled to financial benefits (e.g. lump-sum or royalties) stemming from the exploitation of the
invention ... An expert is required to declare such an interest if the patent is owned by the individual
or if the individual is directly a beneficiary of the exploitation of the patent ... The Agency’s Executive
Director Prof Rasi is indeed mentioned on a number of patents, even beyond those referred to in
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footnote 15 of your complaint letter, but only as inventor, not as owner of the patents. Prof Rasi
does not own any patent together with Sigma-Tau. He is named as inventor on 2 patent families for
which Sigma-Tau is named as applicant or patentee. He is not even the beneficiary of those patent
families. Hence there was and there is no obligation for him to declare these patents in his DoI as
EMA staff member in accordance with EMA’s proceedings on the handling of DoIs ... We would also
like to clarify that Prof Rasi has never worked with or for Sigma-Tau and that no former Sigma-Tau
employee joined EMA since 2011 with the exception of Mr S. Marino, who was indeed the former
General Counsel at Sigma-Tau, as publicly announced by EMA when he was hired after a very
rigorous competition run by a selection panel featuring also external members from the Legal
Service of the European Commission. Prof Rasi was not part of that selection panel and he did not
know Mr Marino when he was still working in industry ... Taking into account the seriousness of the
accusations made via the Internet and the echo that these allegations have had worldwide, EMA
reserves the right to protect its reputation through all appropriate means.”
Wathion wrote that, “A reply to the other issues you have raised in your complaint letter is being
finalised and will be provided to you within the next few days.” We therefore decided not to reply to
Wathion’s letter separately but to wait for the EMA’s main reply to us. However, we did not receive
the main reply before the holiday season had started for some of us.
On 8 July, Guido Rasi’s lawyers, Carter-Ruck solicitors in London, which describe themselves as "One
of the UK's best-known law firms, Carter-Ruck has a longstanding reputation for its expertise in the
field of litigation and dispute resolution," sent us a letter. Their letter alleged that our comments
about Rasi were “highly defamatory” and stating that a consequence of our letter should have been
that, “Mr Marino, far from securing his role at EMA through proper and transparent means and
solely on merit, is strongly to be suspected of having benefited from nepotism and improper
patronage on the part of Professor Rasi.” The lawyers wrote that “in Professor Rasi’s case, he had
never, and does not, have any economic rights or financial interest or benefit (whether actual or
potential) in, or arising from, any of the patents to which the Publication refers. That being the case,
Professor Rasi was and is not under any obligation to declare his status as a mere inventor of certain
patents in his EMA declaration of interests; indeed it would make no sense for him to do so.” The
lawyers made it clear that their client did not wish to become embroiled in a legal dispute but that
he hoped that we would agree “to amend the relevant passages of the Publication, and to publish (in
terms to be agreed) a suitable statement of correction and apology withdrawing these false
allegations.”
Because of holidays, we could not respond before 12 August. We explained that, as researchers, we
believed it would be wrong to change published documents. If errors are detected in scientific
papers, the papers are not changed but errata are published separately. We had therefore written a
separate document, which we attached and aimed to publish on the Nordic Cochrane Centre’s
website, alongside our complaint to the EMA from 26 May. In this document, we described the
issues in detail, apologized for the mistakes, and explained: “We were not aware of the legal
subtleties and assumed that an inventor of a patented technology is also an owner of that patent, as
it is highly unusual that inventors give away their patents to drug companies without benefiting from
them and without having any working relationship with that particular company. As concerns the
employment of people, there are legal procedures to follow, but it is also very common that the
employer contacts people informally, encouraging them to apply for the post.”
51

On 18 August, the lawyers wrote that Rasi could not accept our wording and they sent a revised
version, which they trusted was uncontroversial. We found that version unacceptable because we
were asked to accept statements as facts, although we had had no possibility of checking these facts
ourselves (see below).
On 25 August, we wrote that an apology is a very personal thing, and that, in our opinion, the person
asking for an apology should not require a particular text or format, as the apology would then not
be genuine. We tried to compromise but made it clear that we also needed to protect our own
reputations and therefore needed to explain to the readers of the document that our mistakes were
made in good faith. Therefore, we could not accept that our explanations had been deleted. We also
noted that these explanations were helpful for the readers of the document and therefore had
general public interest, and we added that both the EMA and ourselves serve the public interest.
Finally, we asked the lawyers to take into account that four of us are scientists and the fifth is a
politician. In these capacities, we can write what others have told us, making it clear that this is what
they told us, but we cannot allow ourselves to be forced to accept such statements as fact when we
have had no possibility of checking these facts ourselves.
We proposed that our apology should include our explanations adding:
“Noel Wathion has explained to us that Professor Rasi is not the owner of the patents for which he is
named as inventor” and “The EMA has stated to us that Professor Rasi did not bring anyone to EMA
from Sigma-Tau and that Stefano Marino was recruited according to the ordinary, rigorous EU
selection procedures and received no favourable treatment at all."
We were convinced that this would settle the issue. But on 24 August, the law firm wrote: “Our
client considers that the wording of the errata document is most of the way there, albeit it is still not
acceptable in its current form. Rather that engage in further protracted correspondence, we propose
a telephone discussion to try to resolve any remaining issues. Please confirm if you are amenable to
this approach, and if so please let us know when would be convenient.”
Given our experience with lawyers, we responded: “We prefer to communicate in writing.”
On 7 September, we received a letter from the lawyers saying again that the wording in our
document “is most of the way there.” However, some important issues remained. We needed to
reiterate that we cannot be forced to accept statements as fact when we have had no possibility of
checking these facts ourselves. We furthermore said that lawyers know very well that, in court cases,
one cannot force people to accept and declare what others tell them is the truth. We therefore
could not accept the suggested amendments, which included this sentence: “On the basis of these
assurances we accept that Professor Rasi has never had, and does not have, any economic rights or
financial interest or benefit (whether actual or potential) in, or arising from, any of the patents to
which the Publication refers.”
On 16 September, we received another letter from the lawyers requesting that we should insert this
sentence: “We acknowledge Mr Wathion's statement that Professor Rasi has never had, and does
not have, any economic rights or financial interest or benefit (whether actual or potential) in, or
arising from, any of the patents to which the Publication refers.”
52

We responded that, “Firstly, your suggested amendment misses the context. Secondly, Wathion has
never made any such statement to us; this statement was made by Rasi’s lawyers, Carter-Ruck
solicitors. Thirdly, the amendment is not necessary, as we had already previously acknowledged
Wathion’s explanations.”
On 30 September, we received the 8th letter from Rasi’s lawyers, which said that “Our client is
prepared to accept your proposed wording of the apology, as it is imperative that the public is
alerted as to the true state of matters, and in addition he has no desire to engage further in
protracted correspondence and mutual inconvenience.”
This ended a protracted correspondence that started almost three months earlier. We uploaded our
apology (see the Appendix), which noted that we had submitted a complaint to the EU ombudsman
over maladministration at the EMA related to safety of the HPV vaccines the same day.
We did not at any point in time hear from Rasi himself, only from his deputy and his law firm. We
find the EMA’s various arguments in relation to Rasi’s declaration of interests untenable. Whatever
the rules are, a top executive in an EU institution should ensure that not the slightest suspicion can
be raised that he failed to declare his conflicts of interest. A rule of thumb that is often quoted and
used is that if a normal person would be embarrassed if real or possible conflicts of interest were
revealed that had not been declared, then it was wrong not to declare them. Rasi failed this simple
and sensible test. We therefore rejected the EMA’s and the law firm’s common sense explanations.
The EMA argued that “neither the applicable rules, nor considerations of common sense oblige EMA
staff to declare in their DoI any patents for which they are the inventor/s, but not the owner/s,
unless the inventor is entitled to financial benefits.” And Rasi’s lawyers explained that, “Professor
Rasi was and is not under any obligation to declare his status as a mere inventor of certain patents in
his EMA declaration of interests; indeed it would make no sense for him to do so.”
It would have made a lot of sense for Rasi to declare this, also considering that Rasi is Italian and
Sigma-Tau is an Italian drug company. It is extremely unusual for inventors to give away their patents
to a drug company without benefiting from them in one way or another and without having any
working relationship with that particular company. It is so unusual that we had never heard of any
such case before we were told that this was the case for Rasi. Another reason why it would have
made sense for Rasi to declare his patent inventions has to do with the legitimacy of the EMA in the
public eye. The general public has so little confidence in the drug industry that it is similar to the
confidence they have in tobacco companies and automobile repair shops (11). Furthermore, the
general public has been informed in newspaper articles and TV documentaries that corruption at the
upper levels of drug agencies occurs. The corruption has included several commissioners of the US
Food and Drug Administration (11). FDA commissioner Lester Crawford approved Vioxx, a deadly
arthritis drug from Merck that is estimated to have killed 120,000 people (11), and he left the agency
after Merck had withdrawn Vioxx from the market. After resigning, Crawford became senior council
for Merck’s PR firm, Policy Directions Inc. He later received a fine of $90,000 for falsely reporting he
had sold stock in companies regulated by the FDA while he still owned the shares. These companies
included Pepsico, which sells soft drinks and junk food that make people obese, and at the same
time, Crawford was head of FDA’s obesity working group. Such cases illustrate why top executives in
drug agencies should declare even remotely, possible conflicts of interest, which might raise
suspicion if not declared.
53

Final remarks
The EMA should have considered that when doctors first alerted the scientific community to the
possibility that Pandemrix, one of the influenza vaccines used during the 2009-2010 pandemic, could
be related to the occurrence of narcolepsy in children and adolescents with a specific tissue type, the
reaction was to ridicule these doctors. It has now been firmly established that Pandemrix can cause
narcolepsy, a very serious condition, up to several years after vaccination of children and
adolescents, and that this disease is immune-mediated. However, there was nothing about this,
neither in the EMA’s official report (2), nor in its confidential report (4).
The bottom line for the EMA seems to have been that the vaccine should be protected from criticism
at all costs because it is believed to save lives. One sign of this is that the text in the official report is
nearly identical to the assessments of the rapporteur and the companies.
Sloppy science, combined with unprofessional and unfair criticism of independent research, such as
the one the EMA raised against the diligent Danish researchers, is a serious threat to scientific
progress and public health. Those who raise concerns should be complemented for their courage,
even if their suspicions are later shown to be wrong. Indeed, it is a requirement by DMHA that
Danish doctors raise concerns they might have. Unfounded criticism of whistleblowers from those at
the top of overseeing agencies is potentially highly damaging, as it may prevent important concerns
from being raised. Brinth reported in her “responsum” that she had been contacted by quite a few
doctors and researchers from various countries who shared her concerns and had seen the same
pattern, but that most of them were afraid to speak up (5, p51). She found that we have established
a culture where it is not acceptable to have a critical approach towards vaccines. This could create
much greater problems than declining uptake rates in HPV vaccination programmes. Should the
concerns over possible serious harms of the HPV vaccine be confirmed, the trust in the EMA and in
vaccines in general may be damaged beyond repair.
Since we submitted our complaint to the EMA on 26 May 2016, we have been made aware of several
upcoming studies that provide data in support of the autoimmune causal theory (23; see also the
discussion section in this paper). It is possible that most seriously ill girls suffer from an autoimmune
disorder, and not from a functional disorder (i.e. a psychiatric disorder), as has been proposed. These
upcoming data cannot prove that it was the HPV vaccines that caused the serious harms, but it
should be a research priority to find out.
The secrecy imposed by the EMA on its committee members is not in the public interest. Drug
regulators tend to have a narrow vision, either because of their remit or because they have become
too close to the drug industry through their daily work, which often involves contacts with the
industry, and by employment of people with long careers in the industry. We hope the ombudsman
will ask the EMA to halt this practice.
Public health is about the promotion of health and prevention of disease and disability through the
organised efforts of society. This entails protection from harms and involves progression of
knowledge in open collaboration. As far as we can see, the actions of the EMA in this case indicates
that the agency is more concerned about protecting its own previous decisions and the vaccines than
about protecting the citizens and giving them the option of choosing for themselves whether or not
they would like to get vaccinated or have their children vaccinated against HPV. Citizens don’t
54

appreciate a paternalistic statement that all is fine based on inscrutable research conducted by the
drug companies (2). Most girls and women will get vaccinated, but some will prefer to avoid the
vaccine, even if the risk of serious harm is very small. Others will prefer screening instead.
We wrote in our complaint to the EMA that all available material about suspected harms of a public
health intervention directed towards healthy children, including intermediate reports, should be
accessible to anyone. The EMA’s internal report (4) and all other documents related to this case
should therefore be made publicly available, without redactions. We also noted that we did not find
any commercially confidential information anywhere in the documents we reviewed. The EMA’s
procedures for evaluating the safety of medical interventions need to be fundamentally reworked
and made transparent to the public.
Finally, our societies should no longer accept that assessments of drug safety are left to companies
with huge financial interests and to a drug regulator that receives 80% of its funding from the drug
industry (49) and allows experts with financial conflicts of interest in relation to the companies to
guide them. In court cases, jurors are carefully selected to avoid bias. The same principle should
apply to experts who make decisions that have consequences for our health and survival.
We will end by quoting Silvio Garattini, a former Italian representative at the EMA, who published a
paper in BMJ in 2016 with the title: “The European Medicines Agency is still too close to industry:
Two decades after its inception, the agency still fails to put patients’ interests first” (49).
References
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Complaint to the European Medicines Agency (EMA) over maladministration at the EMA. 26 May
2016. Available at http://nordic.cochrane.org/research-highlights.
2 European Medicines Agency. Assessment report. Human papilloma virus (HPV) vaccines. 11
November 2015 (40 pages).
3 Danish Health and Medicines Authorities. EMA's new assessment of the HPV vaccine: The benefits
outweigh the risks. 17 April 2015. https://sundhedsstyrelsen.dk/en/news/2015/emas-newassessment-of-the-hpv-vaccine-the-benefits-outweigh-the-risks.
4 Briefing note to experts. EMA/666938/2015. 13 October 2015 (256 pages).
5 Brinth L. Responsum to Assessment Report on HPV-vaccines released by EMA November 26th
2015. 17 December 2015. http://www.ft.dk/samling/20151/almdel/suu/bilag/109/1581470.pdf.
6 Regulation (EC) No 1049/2001 of the European Parliament and of the Council of 30 May 2001
regarding public access to European Parliament, Council and Commission documents. Official Journal
of the European Communities 2001; L145: 43-8.
www.europarl.europa.eu/RegData/PDF/r1049_en.pdf.
7 Letter from Noël Wathion to Peter C Gøtzsche, 17 June 2016 (available in Appendix).
55

8 Letter from Noël Wathion to Peter C Gøtzsche, 1 July 2016 (available in Appendix).
9 Letter from Carter-Ruck solicitors on behalf of their client, Guido Rasi, to Peter C Gøtzsche, 8 July
2016 (available in Appendix).
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Reports, and Published Papers of Trials of Orlistat: A Document Analysis. PLoS Med 2016; 13:
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13 Diamandouros PN. Ombudsman: European Medicines Agency should disclose clinical
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14 Hawkes N. Lobby groups call for closure of ‘revolving door’ between drug regulators and
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15 Jefferson T, Jørgensen L. Human Papilloma Virus (HPV) vaccines, Complex Regional Pain Syndrome
(CRPS), Postural Orthostatic Tachycardia Syndrome (POTS), and autonomic dysfunction: a review of
the regulatory evidence from the European Medicines Agency (EMA). Indian J Med Ethics 2016
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16 Gøtzsche PC. Deadly psychiatry and organised denial. Copenhagen: People’s Press; 2015.
17 Trojaborg K. Danske forskere sables ned: Ingen sammenhæng mellem HPV vaccine og alvorlige
symptomer. Politiken 2015 Nov 26.
18 EMA. Article 20 referral, HPV vaccines- ASK-20511- Release letter to the requester. 2016 June 9.
19 Watson R. European ombudsman questions European Medicines Agency over AbbVie redactions.
BMJ 2014; 349: g6904.
20 Gøtzsche PC. AbbVie considers harms to be commercially confidential information: sign a
petition. BMJ 2013; 347: f7569.
21 Tom Jefferson et al: EMA’s data sharing policy - towards peeping tom based medicine? BMJ 2014;
22 May. http://blogs.bmj.com/bmj/2014/05/22/tom-jefferson-et-al-emas-data-sharing-policytowards-peeping-tom-based-medicine/
22 Tom Jefferson and Peter Doshi: EMA’s double U-turn on its Peeping Tom policy for data release.
BMJ 2014; 13 June. http://blogs.bmj.com/bmj/2014/06/13/tom-jefferson-and-peter-doshi-emasdouble-u-turn-on-its-peeping-tom-policy-for-data-release/
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23 Chandler RE, Juhlin K, Fransson J, Caster O, Edwards R, Noren GN. Current safety concems with
human papillomavirus vaccine: a cluster analysis of reports in Vigibase (R). Drug Saf 2016 Sept 16.
24 Minutes and responses to PRAC from the SAG Vaccines meeting on HPV vaccines (Article 20
referral) (GlaxoSmithKline biologicals, Sanofi Pasteur, Merck). 21 October 2015, 9:30-15:30 - Room
2F - Chair: Prof Andrew Pollard. London, 4 Nov 2015. Doc. Ref.: EMA/702401/2015. Confidential.
25 PRAC co-rapporteur’s referral updated assessment report. Updated report circulated 28 October
2015.
26 Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions
Version 5.1.0. The Cochrane Collaboration, 2011.
27 Dunder K, Mueller-Berghaus J. Rapporteurs’ Day 150 Joint Response Assessment Report. Gardasil
9. 2014 Nov 23.
28 Weber C, Andersen S. Firma bag HPV-vaccinen underdrev omfanget af alvorlige bivirkninger [The
company behind the HPV vaccine underestimated the prevalence of serious side effects]. Berlingske
2015; 26 Oct.
29 PRAC (co)-rapporteur’s referral 2nd updated preliminary assessment report. Updated report
circulated 28 October 2015.
30 Palshof T. En analyse of EMA’s kritik af 3 danske videnskabelige publikationer vedrørende
rapporterede bivirkninger fra danske piger og kvinder opstået i tilslutning til HPV-vaccination. Et
responsum til offentlig brug - version 3.0. 2015 Dec 10.
31 Nordic Cochrane Centre. Re: Ask-20511, about the safety of the HPV vaccines. 2016 June 10.
32 Sharma T, Guski LS, Freund N, Gøtzsche PC. Suicidality and aggression during antidepressant
treatment: systematic review and meta-analyses based on clinical study reports. BMJ 2016; 352: i65.
33 Bielefeldt A, Danborg P, Gøtzsche PC. Precursors to suicidality and violence on antidepressants:
systematic review of trials in adult healthy volunteers. J R Soc Med 2016 (in press).
34 Maund E, Tendal B, Hróbjartsson A, Jørgensen KJ, Lundh A, Schroll J, Gøtzsche PC. Benefits and
harms in clinical trials of duloxetine for treatment of major depressive disorder: comparison of
clinical study reports, trial registries, and publications. BMJ 2014; 348: g3510.
35 Maund E, Tendal B, Hróbjartsson A, Lundh A, Gøtzsche PC. Coding of adverse events of suicidality
in clinical study reports of duloxetine for the treatment of major depressive disorder: descriptive
study. BMJ 2014; 348: g3555.
36 EMA. Article 20 referral, HPV vaccines - ASK-20823 - Decision letter to the requester -
confirmatory application. 2016 July 11.
57

37 Wikipedia. Duilio Poggiolini. Available online at: http://en.wikipedia.org/wiki/Duilio_Poggiolini
(accessed 10 November 2012).
38 Abbott A. Italian health sector in disarray following more scandals. Nature 1993; 364: 663.
39 Day M. Italian police arrest drug officials over alleged falsification of data. BMJ 2008; 336:
1208–9.
40 Flere vælger HPV-vaccine fra - flere vil dø af livmoderkræft. BT 2016 May 6.
41 Ioannidis JPA, Evans SJW, Gøtzsche PC, O’Neill RT, Altman DG, Schulz K, Moher D, CONSORT
Group. Better Reporting of Harms in Randomized Trials: An Extension of the CONSORT Statement.
Ann Intern Med 2004; 141: 781-8.
42 Jefferson T, Jones MA, Doshi P, Del Mar CB, Hama R, Thompson MJ, Spencer EA, Onakpoya IJ,
Mahtani KR, Nunan D, Howick J, Heneghan CJ. Neuraminidase inhibitors for preventing and treating
influenza in adults and children. Cochrane Database of Systematic Reviews 2014, Issue 4. Art. No.:
CD008965.
43 Maund E. The effect of selective serotonin reuptake inhibitors (SSRIs) on suicidality and violent
behaviour. PhD thesis. University of Copenhagen 2015; June 28: pages 89-90. Available from:
http://nordic.cochrane.org/research-highlights.
44 [Hearing in the Danish Parliament about the safety of HPV vaccines]. Dec 17, 2005.
http://www.ft.dk/webtv/video/20151/suu/tv.3040.aspx?i=2015-12-17T15.
45 Anderson H. Is HPV vaccine safe? Hainault mum says daughter’s chronic fatigue is linked to cancer
drug. Ilford Recorder 2015 Sept 24.
46 Guido Rasi. EMA Public Declaration of Interests. 20 July 2015.
http://www.ema.europa.eu/docs/en_GB/document_library/Other/2012/02/WC500123382.pdf.
47 Guido Rasi’s patents. http://patents.justia.com/search?q=guido+rasi (downloaded 7 May 2016).
48 Decision on rules relating to Articles 11a and 13 of the Staff Regulations concerning the handling
of declared interests of employees of the European Medicines Agency. 1 February 2012.
EMA/MB/500408/2011.
49 Garattini S. The European Medicines Agency is still too close to industry: Two decades after its
inception, the agency still fails to put patients’ interests first. BMJ 2016; 353: i2412.
58

Appendix. Correspondence related to the declaration of interests for the EMA’s executive director
As noted above on page 50, we believe this correspondence has considerable public interest and we
have therefore decided to include the entire correspondence in the Appendix to this complaint to
the ombudsman.
59

Professor Peter C Gøtsche
Nordic Cochrane Centre
Rigshospitalet, Dept. 7811
Blegdamsvej 9
2100 Copenhagen
DENMARK
17 June 2016
EMA/397114/2016
Deputy Executive Director
Dear Prof Gøtzsche
Subject: Your letter of complaint dated 26 May 2016 to the European Medicines Agency (EMA) over
maladministration at the EMA.
I refer to your letter of complaint sent to Prof Rasi relating to maladministration at EMA. This reply only
deals with point 4 of the section “Conflicts of interest” and a number of allegations on page 17 in the
section “Final remarks” in your complaint letter. A reply to the other issues you have raised in your
complaint letter is being finalised and will be provided to you within the next few days.
In your complaint you allege that Prof Rasi may have a conflict of interest, stemming from his previous
contacts with industry, and which you claim he failed to declare. Without prejudice to any response
and defence that Prof Rasi may wish to forward to you directly, EMA would like to refute your
unsubstantiated allegations in the strongest possible terms, for the sake of transparency owed to the
general public and to the EU regulatory network of which EMA is an important member.
The Decision on rules relating to Articles 11, 11a and 13 of the Staff Regulations concerning the
handling of declared interests of staff members of the European Medicines Agency and candidates
before recruitment (EMA/622828/2013(revised)) describes the interests in pharmaceutical industry to
be declared by the Agency’s staff. Amongst other things, EMA staff members are required to declare in
their declaration of interests (DoI) any ownership of a patent held for a period of 5 years prior to the
start of employment with the Agency.
As you may be aware (see for instance European IPR Helpdesk), the inventor mentioned on a patent is
the creator of the invention and is always entitled to be designated on the patent, regardless of who
files the patent application or owns the patent. An inventor remains an inventor throughout the term of
a patent, but he is not necessarily the owner of the patent, e.g. the ownership rights may be vested
originally upon, or subsequently assigned to, a subject other than the inventor/s. Only the owner of a
patent can enjoy economic rights with regard to that particular invention. Therefore, neither the
applicable rules, nor considerations of common sense oblige EMA staff to declare in their DoI any
patents for which they are the inventor/s, but not the owner/s, unless the inventor is entitled to
financial benefits (e.g. lump-sum or royalties) stemming from the exploitation of the invention.
30 Churchill Place ● Canary Wharf ● London E14 5EU ● United Kingdom
Telephone +44 (0)20 3660 6000 Facsimile +44 (0)20 3660 5555
Send a question via our website www.ema.europa.eu/contact
An agency of the European Union

The same principle is applicable to European experts. According to the EMA policy on the handling of
declarations of interests of scientific committees’ members and experts (EMA/626261/2014, Corr. 1),
the definition of financial interests encompasses intellectual property rights relating to a medicinal
product, including patents. An expert is required to declare such an interest if the patent is owned by
the individual or if the individual is directly a beneficiary of the exploitation of the patent. If the expert
is the inventor of the patent, but not the owner or beneficiary, there is no obligation to declare it.
The Agency’s Executive Director Prof Rasi is indeed mentioned on a number of patents, even beyond
those referred to in footnote 15 of your complaint letter, but only as inventor, not as owner of the
patents. Prof Rasi does not own any patent together with Sigma-Tau. He is named as inventor on 2
patent families for which Sigma-Tau is named as applicant or patentee. He is not even the beneficiary
of those patent families. Hence there was and there is no obligation for him to declare these patents in
his DoI as EMA staff member in accordance with EMA’s proceedings on the handling of DoIs.
We would also like to clarify that Prof Rasi has never worked with or for Sigma-Tau and that no former
Sigma-Tau employee joined EMA since 2011 with the exception of Mr S. Marino, who was indeed the
former General Counsel at Sigma-Tau, as publicly announced by EMA when he was hired after a very
rigorous competition run by a selection panel featuring also external members from the Legal Service
of the European Commission. Prof Rasi was not part of that selection panel and he did not know Mr
Marino when he was still working in industry. The statements appearing at page 17 of the Nordic
Cochrane complaint against EMA have therefore no foundation.
We trust that the information provided in this letter has adequately addressed the points raised in your
complaint letter. Taking into account the seriousness of the accusations made via the Internet and the
echo that these allegations have had worldwide, EMA reserves the right to protect its reputation
through all appropriate means. Please also note that EMA will publish this reply for the sake of
transparency.
Yours sincerely,
[Signature on File]
Noël Wathion
Deputy Executive Director
CC:
Karsten Juhl Jørgensen, Deputy Director of the Nordic Cochrance Centre, Rigshospitalet
Tom Jefferson, Honorary Research Fellow, Centre for Evidence Based Medicine, Oxford OX2 6GG
Margrete Auken, MEP (The Greens/European Free Alliance)
Louise Brinth, PhD, MD, Danish Syncope Unit, Frederiksberg
EMA/397114/2016 Page 2/2

D irect Email: adam .tudor@carter-ruck .com
D irect Fax: 020 7353 5553
Our Ref: AT/MP/16091.1
Your Ref: EMN408257/ 2016
8 July 201 6
BY EMAlL & POST pcg@cochrane.dk
PRIVATE AND CONFIDENTlAL
Professor Peter C. Gøtzsche
Nordie Cochrane Centre
Rigshospitalet, Dept. 7811
Blegsdamsvej 9
2100 Capenhagen
Denmark
Carter-Rucl<
Dea r Sir
Our Client: Professor Guido Rasi
We aet for Professor Guido Rasi, the Executive Director at the London-based
European Medieines Agency ("EMA").
Our client has consulted us in relation to certain aspeels of a document entitled
"Complaint to the European Medieines Agency (EMA) over maladministration at the
EMA" ("the Publication"), which was published on 26 May 2016 under the banner of
the Nordie Cochrane Centre and sent in your name, along with !hose of a number of
co-signatories.
Carter - Ru c k Soliciters
6 S t Andrew Street
London EC4A 3AE
T 020 7353 5005
F 020 7353 5553
DX 333 Chancery Lane
www.carter-ruckcom
We wish to make clear at the outset that it is not the purpose of this letter to address
those parts of the Publication concerning Nordie Cochrane's critique of EMA in the
context of the latter's Assessment Report of November 2016; we are aware that
those matters have been addressed with you by EMA itself in its letter of 1 July 2016.
However, the Publicatio n contains certain discrete statements (specifically on pages
15 and 17) which are hig hly detarnatory of our client individually, alleging, as they will
have been understood to do:-
• That Professor Rasi has, in breach of his ethical and legal obligations, tailed
to declare his interest in various registered patents.
• That, acting in brazen conflict of inierest and contrary to the basic principles
of transparency and propriety in a public institution such as the EMA,
Professor Rasi recruited a number of individuals, including Stefano Marino,
from Sigma Tau - a company with which (according to the Publication) he
has worked for many years and with which he has close ongoing commercial
inierests in the form of patents.
• Thai in consequence Mr Marino, far from securing his role at EMA throug h
proper and transparent means and solely on merit, is strongly to be
suspected of having benefited from nepotism and improper patronage on the
pa rt of Professor Rasi.
As well as being detarnatory of our client, these allegations are also wholly untrue.
We are informed !hat Noel Wathion of the EMA wrote to you on 17 June 2016,
explaining in detail the baselessness of these allegations. Despite the gravity of
those allegations, the EMA has not received so much as an acknowledgement of Mr
PCRI-2 109366. '
Partners
Alasd>.ir Peppeo
Guy Marlin
NogciTaot
Ruth Collard
Camcror. Do ey
Oaore Goll
AdamTudor
Isabel Marto~ll
Partners hip Seereta ry
Helen Bun·luck
Authoroscd Jnd rcgt~lated
by :hc Solomors Rc~ul,otoon
Autnol'lty
SRA. No ~4769

Wathion's letter, let alone any substantive response or suitable retraction and
cerreetion.
We do not propose in !his letter to repeat in detail what was said in Mr Wathion's letter,
a copy of which we attach for your further reference. Suffice it to say that there is
simply no basis for alleging that Professor Rasi has in any way tailed to comply with
his obligation to declare interests.
lt is clear that in publishing these false allegations concerning Professor Rasi, you
tailed to properly scrutinise the applicable EMA policies and rules on deelaraliens of
interest, or to understand the basic technicalities and nomenelature of patent
registration. Had you done so (or had you taken the trouble to conlaet Professor Rasi
before publishing these serious misstatements) then you would have been aware that,
while Professor Rasi has indeed been Iisted on a number of patent regisirations within
the past five years, that is solely as an inventar, not as owner.
While the inventar will always be Iisted in the regisiration material throughout the
period of the patent, it certainly does not automatically follow that he or she is the
owner of the patent or might in any way benefil from it financia lly. Thus, in Professor
Rasi's case, he has never, and does not, have any economic rights or financial
inierestor benetit (whether actual or potential) in, or arising from, any of the patents to
which the Publication refers.
That being the case, Professor Rasi was and is not underanyobligation to declare his
status as a mere inventer of certain patents in his EMA declaration of interests; indeed
it would make no sense for him to do so.
To make matters worse, in the penultimate paragraph on page 17 of the Publication,
you clearly seek to suggest that, acting in flagrant conflict of inierest (if not corruptly)
Professor Rasi "brought in" (ie recruited) "a number of people", including Mr Marino,
from Sigma Tau - a company with whom, you suggest, Professor Rasi has or has had
a commercial relationship.
Once again, these allegations are completely unfounded. As Mr Wathion has already
made clear and as we have alluded to above, Professor Rasi does not "own any
patents with" Sigma Tau. He is registered simply as an inventar in respect of two
patent families of which Sigma Tau was applicant or patentee. He has no financial or
other inierest (whether actual or potential) in these patents. Nor Ilas Professor Rasi
ever "worked with" Sigma Tau, as you assert.
lt is similarly untrue for you to assert thai Professor Rasi "brought in" people from
Sigma Tau. We note in passing that, while easting !his (false) aspersion in general
terms, the Publication does not cite any name other than Mr Marino. Yet, as Mr
Wathion has already made clear, Professor Rasi played no part whatsoever in the
selection or recruitment of Mr Marino or indeed anyone elsefrom Sigma Tau; indeed,
Professor Rasi did not even know Mr Marino when he was working at that company.
Mr Marino was recruited entirely on merit and in accordance with the relevant
procedures; for you to suggest otherwise is as false as it is darnaging to the
professional reputations bot11 of Professor Rasi and Mr Marino.
As you will appreciate, the publication of these serious, yet wholly false, allegations is
extrernely damaging to our client's professional and personal reputation, going to the
heart of his integrity and unjustifiably easting doubt on his compliance with his legal
obligations and on his professionalism and ethics. Similarly, Mr Marino is a lawyer of
some 30 years' standing; for a body such as Nordie Cochrane to (falsely) impute that
he secured his current role through questionable and quite possibly corrupt means, is
wholly unjustified and highly damaging.
Our client has asked us to stress that he recognises and respects the importance of
NGOs such as Nordie Cochrane being free to subject to scrutiny and call to account
the activities of public authorities such as the EMA and other bodies performing an
f'CRI -21093661 2
Carter-Rud

important role in publ ic health, provided those criticisms are published reasonably and
in good faith. However, there can be no justifi cation whatsoever for publisiling serious
libels concerning individuals in the manner complained of in this letter, particularly in
circumstances where you made no effort whatsoever to put these allegations to our
client befare publication.
Less justifiable still is your decision to publish these falsehoods to the world online at
http://nordic.cochrane.org/sites/nordic.cochrane.org/files/uploads/ResearchHighlights/
Complaint-to-EMA-over-EMA.pdf, where they will no doubt have been (and, if
uncorrected, will in future be) viewed by a large number of individuals worldwide,
including in the UK (where our client lives and works, and where EMA and, as we
understand it, yo ur umbrella organisation is based). Our client is also concerned to
note that the Publicalian has, inevitably, also been pieked up by at least one other
website, and which makes specific reference to the personal allegations which are the
subject of this letter:
http://www.activi stpost.com/2016/06/prestigious-eoehrane-ehallenges-the-europeanmedieines-ageney-about-hpv-vaecines-harrns.html
We wish to make clea r that our client has no wish to beeome embroiled in a legal
dispute, whether with the Nordie Coehrane Centre or with you as the author of the
Publieation . However, our client hopes that you will appreeiate that, sueh is the
seriousness of these allegations, he eannot allow them to go unehallenged or
uneorreeted. He also hopes that, as a reputable and purportedly responsible
organisa tion, you will agree immediately to arnend the relevant passages of the
Publication, and to publish (in terms to be agreed) a suitable statement of cerreetion
and apology withdrawing these false allegations.
We look forward to hearing from yo u within 1 O days o f the date of this letter. In the
meantime we must expressly reserve all of our client's rights.
Yours faithfully
C- f2---
Carter-Ruck
Carter-Rud<
PCRI·2109366.1 3

Direct Email: adam.tudor@carter-ruck.com
Direct Fax: 020 7353 5553
O ur Ref: AT/MP/16091.1
Your Re f: EMA/408257/20 16
21 July 2016
BY EMAIL & POST pcg@cochrane.dk
PRIVATE AND CONFIDENTIAL
Professor Peter C. Gøtzsche
Nordie Cochrane Centre
Rigshospitalet, Dept. 7811
Blegsdamsvej 9
2100 Capenhagen Ø,
Denmark
Carter-Ruet<
Dear Sir
Our Client: Professor Guido Rasi
We refer to our letter dated 8 July 2016, a further copy of which is enclosed for you r
ease of reference.
We note that we have not had the courtesy of an acknowledgment of receipt of our
letter, still less the substantive response which we had requested be provided by the
beginning of this week.
May we piease now hear from you in full , without delay.
Carter- Ruck Soliciter s
6 St Andrew Street
London EC4A 3AE
T 020 7353 5005
F 020 7353 5553
DX 333 Chancery Lane
www.carter-ruck.com
Yours faithfully
c~~ ~
Carter-Ruck
Partners
Alasdair Pepper
Guy Martin
NigelTalt
Ruth Collard
Cameron Doley
Claire Glll
AdamTude r
Isabel Marto reli
Partnership Secretary
Helen Burrluck
PCRI-2 120746.1
Authonsed and regulated
by the Solicita rs Regulat>on
Authority
SRA No. 44769

D irect Email: adam .tudor@carter-ruck .com
D irect Fax: 020 7353 5553
Our Ref: AT/MP/16091.1
Your Ref: EMN408257/ 2016
8 July 201 6
BY EMAlL & POST pcg@cochrane.dk
PRIVATE AND CONFIDENTlAL
Professor Peter C. Gøtzsche
Nordie Cochrane Centre
Rigshospitalet, Dept. 7811
Blegsdamsvej 9
2100 Capenhagen
Denmark
Carter-Rucl<
Dea r Sir
Our Client: Professor Guido Rasi
We aet for Professor Guido Rasi, the Executive Director at the London-based
European Medieines Agency ("EMA").
Our client has consulted us in relation to certain aspeels of a document entitled
"Complaint to the European Medieines Agency (EMA) over maladministration at the
EMA" ("the Publication"), which was published on 26 May 2016 under the banner of
the Nordie Cochrane Centre and sent in your name, along with !hose of a number of
co-signatories.
Carter - Ru c k Soliciters
6 S t Andrew Street
London EC4A 3AE
T 020 7353 5005
F 020 7353 5553
DX 333 Chancery Lane
www.carter-ruckcom
We wish to make clear at the outset that it is not the purpose of this letter to address
those parts of the Publication concerning Nordie Cochrane's critique of EMA in the
context of the latter's Assessment Report of November 2016; we are aware that
those matters have been addressed with you by EMA itself in its letter of 1 July 2016.
However, the Publicatio n contains certain discrete statements (specifically on pages
15 and 17) which are hig hly detarnatory of our client individually, alleging, as they will
have been understood to do:-
• That Professor Rasi has, in breach of his ethical and legal obligations, tailed
to declare his interest in various registered patents.
• That, acting in brazen conflict of inierest and contrary to the basic principles
of transparency and propriety in a public institution such as the EMA,
Professor Rasi recruited a number of individuals, including Stefano Marino,
from Sigma Tau - a company with which (according to the Publication) he
has worked for many years and with which he has close ongoing commercial
inierests in the form of patents.
• Thai in consequence Mr Marino, far from securing his role at EMA throug h
proper and transparent means and solely on merit, is strongly to be
suspected of having benefited from nepotism and improper patronage on the
pa rt of Professor Rasi.
As well as being detarnatory of our client, these allegations are also wholly untrue.
We are informed !hat Noel Wathion of the EMA wrote to you on 17 June 2016,
explaining in detail the baselessness of these allegations. Despite the gravity of
those allegations, the EMA has not received so much as an acknowledgement of Mr
PCRI-2 109366. '
Partners
Alasd>.ir Peppeo
Guy Marlin
NogciTaot
Ruth Collard
Camcror. Do ey
Oaore Goll
AdamTudor
Isabel Marto~ll
Partners hip Seereta ry
Helen Bun·luck
Authoroscd Jnd rcgt~lated
by :hc Solomors Rc~ul,otoon
Autnol'lty
SRA. No ~4769

Wathion's letter, let alone any substantive response or suitable retraction and
cerreetion.
We do not propose in !his letter to repeat in detail what was said in Mr Wathion's letter,
a copy of which we attach for your further reference. Suffice it to say that there is
simply no basis for alleging that Professor Rasi has in any way tailed to comply with
his obligation to declare interests.
lt is clear that in publishing these false allegations concerning Professor Rasi, you
tailed to properly scrutinise the applicable EMA policies and rules on deelaraliens of
interest, or to understand the basic technicalities and nomenelature of patent
registration. Had you done so (or had you taken the trouble to conlaet Professor Rasi
before publishing these serious misstatements) then you would have been aware that,
while Professor Rasi has indeed been Iisted on a number of patent regisirations within
the past five years, that is solely as an inventar, not as owner.
While the inventar will always be Iisted in the regisiration material throughout the
period of the patent, it certainly does not automatically follow that he or she is the
owner of the patent or might in any way benefil from it financia lly. Thus, in Professor
Rasi's case, he has never, and does not, have any economic rights or financial
inierestor benetit (whether actual or potential) in, or arising from, any of the patents to
which the Publication refers.
That being the case, Professor Rasi was and is not underanyobligation to declare his
status as a mere inventer of certain patents in his EMA declaration of interests; indeed
it would make no sense for him to do so.
To make matters worse, in the penultimate paragraph on page 17 of the Publication,
you clearly seek to suggest that, acting in flagrant conflict of inierest (if not corruptly)
Professor Rasi "brought in" (ie recruited) "a number of people", including Mr Marino,
from Sigma Tau - a company with whom, you suggest, Professor Rasi has or has had
a commercial relationship.
Once again, these allegations are completely unfounded. As Mr Wathion has already
made clear and as we have alluded to above, Professor Rasi does not "own any
patents with" Sigma Tau. He is registered simply as an inventar in respect of two
patent families of which Sigma Tau was applicant or patentee. He has no financial or
other inierest (whether actual or potential) in these patents. Nor Ilas Professor Rasi
ever "worked with" Sigma Tau, as you assert.
lt is similarly untrue for you to assert thai Professor Rasi "brought in" people from
Sigma Tau. We note in passing that, while easting !his (false) aspersion in general
terms, the Publication does not cite any name other than Mr Marino. Yet, as Mr
Wathion has already made clear, Professor Rasi played no part whatsoever in the
selection or recruitment of Mr Marino or indeed anyone elsefrom Sigma Tau; indeed,
Professor Rasi did not even know Mr Marino when he was working at that company.
Mr Marino was recruited entirely on merit and in accordance with the relevant
procedures; for you to suggest otherwise is as false as it is darnaging to the
professional reputations bot11 of Professor Rasi and Mr Marino.
As you will appreciate, the publication of these serious, yet wholly false, allegations is
extrernely damaging to our client's professional and personal reputation, going to the
heart of his integrity and unjustifiably easting doubt on his compliance with his legal
obligations and on his professionalism and ethics. Similarly, Mr Marino is a lawyer of
some 30 years' standing; for a body such as Nordie Cochrane to (falsely) impute that
he secured his current role through questionable and quite possibly corrupt means, is
wholly unjustified and highly damaging.
Our client has asked us to stress that he recognises and respects the importance of
NGOs such as Nordie Cochrane being free to subject to scrutiny and call to account
the activities of public authorities such as the EMA and other bodies performing an
f'CRI -21093661 2
Carter-Rud

important role in publ ic health, provided those criticisms are published reasonably and
in good faith. However, there can be no justifi cation whatsoever for publisiling serious
libels concerning individuals in the manner complained of in this letter, particularly in
circumstances where you made no effort whatsoever to put these allegations to our
client befare publication.
Less justifiable still is your decision to publish these falsehoods to the world online at
http://nordic.cochrane.org/sites/nordic.cochrane.org/files/uploads/ResearchHighlights/
Complaint-to-EMA-over-EMA.pdf, where they will no doubt have been (and, if
uncorrected, will in future be) viewed by a large number of individuals worldwide,
including in the UK (where our client lives and works, and where EMA and, as we
understand it, yo ur umbrella organisation is based). Our client is also concerned to
note that the Publicalian has, inevitably, also been pieked up by at least one other
website, and which makes specific reference to the personal allegations which are the
subject of this letter:
http://www.activi stpost.com/2016/06/prestigious-eoehrane-ehallenges-the-europeanmedieines-ageney-about-hpv-vaecines-harrns.html
We wish to make clea r that our client has no wish to beeome embroiled in a legal
dispute, whether with the Nordie Coehrane Centre or with you as the author of the
Publieation . However, our client hopes that you will appreeiate that, sueh is the
seriousness of these allegations, he eannot allow them to go unehallenged or
uneorreeted. He also hopes that, as a reputable and purportedly responsible
organisa tion, you will agree immediately to arnend the relevant passages of the
Publication, and to publish (in terms to be agreed) a suitable statement of cerreetion
and apology withdrawing these false allegations.
We look forward to hearing from yo u within 1 O days o f the date of this letter. In the
meantime we must expressly reserve all of our client's rights.
Yours faithfully
C- f2---
Carter-Ruck
Carter-Rud<
PCRI·2109366.1 3

EUROPEAN i\ttEDiCINES AGENCY
•\ l l \) l C l N l :>
l i l ,\ l. l Il
Professor Peter C Gøtsche
Nordie Cochrane Centre
Rigshospitalet, Dept. 781 1
Blegdamsvej 9
2100 Capenhagen
DENMARK
17 June 2016
EMA/397114/2016
Oeputy Executive Director
Dea r Prof Gøtzsche
Subject: Your letter of complaint dated 26 May 2016 to the European Med ieines Agency (EMA) over
maladministration at the EMA.
I refer to your letter of complalnt sent to Prof Rasi relating to maladministration at EMA. This reply only
deals with point 4 o f the section "Conflicts of interest" and a number o f allegations o n page 17 in the
section "Final remarks" in your complaint letter. A reply to t he ether issues you have ralsed in your
complaint letter is being finalised and will be provided to you within the next few days.
In your complaint you allege that Prof Rasl may have a confilet of interest, stemming from his previous
contacts with industry, and which you claim he failed to declare. Without prejudice to any response
and defence that Prof Rasi may wish to forward to you directly, EMA would like to refute your
unsubstantiated allegations in the strengest possible terms, for the sake of transparency owed to the
general public and to the EU regulatory network of which EMA is an important member.
The Decision on rules retating to Artides 11, 11a and 13 of the Staff Regulations concerning the
handling of declared interests of staff members of the European Medieines Agency and eandidates
before recruitment (EMA/622828/2013(revised)) describes the interests in pharmaceutical industry to
be d edared by the Ag eney's staff. Amongst ether t hings, EMA staff members a re required to declare in
their deelaratic n of interests (Do!) a ny ownership of a patent held for a period of 5 years prior to the
start of employment with the Agency.
As you may be aware (see for instance Europe an IPR H e l~, the inventar menticned on a patent is
the creator of the invention and is always entitled to be designated on the patent, regardless of who
files the patent application or owns the patent. An inventer remains an inventar throughout the term of
a patent, but he is not necessarily the owner of the patent, e.g. the ownership rights may be vested
originally upon, or subsequently assigned to, a subject ether than the inventar/s. Only the owner of a
patent can enjoy economic rights with regard tothat particu lar invention. Therefore, neither the
a ppilea ble rul es, nor considerations of common sense oblige EMA staff to declare in t heir Do! any
patents for which they are t he inventar/s, but not the owner/s, unless the inventer isentitled to
financlal benefits (e .g. lump-sum or royalties) stemming from t he exploitation of the invention.
JO (.IL.m.:li l!l r ... lt.:ce: • (.(llld r )' V/h,,: f • l CJndGil Il 'l ')t !J • Ll'11 l~.,c l K !111d01n
Telephone ; ·1'1 (1.l)hJ 1L60 0000 Facsimile 1 ~ · l (O)?.Il 'l G60 :,s~:.
Send a qucstion via our wcbsite WW\'o'. ntc:L t

The same principle is applicable to European experts. According to the EMA policy on the handl ing of
declarations of interests of scientific committees' members and experts (EMA/626261/2014, Corr. l},
the definition of financial interests enearnpasses intellectual property rights relating to a medicinal
product, including patents. An expert is required to declare such an interest if t he patent is owned by
the individual or if the individual is directly a beneficiary of the exploitation of the patent. !f the expert
is the inventer of the patent, but not the owner or beneficiary, there is no obligation to declare it.
The Agency's Executive Director Prof Rasi is indeed menticned on a number of patents, even beyond
those refe rred to in footnote 15 of your complaint letter, but only as inventar, not as owner of the
patents. Prof Rasi does not own anypatent together with Sigma-Tau. He is narned as inventar on 2
patent families for which Sigma-Tau is n a med as applicant o r patentee . H e is not e ven the beneficiary
of those patent families. Hence there was and there is no obligation for hi m to declare these patents in
his Do! as EMA staff member in accordance with EMA's proceedings on the handling of Dols.
W e would al so like to clarify that Prof Rasi has never worked with o r for Sigma-Tau and that no former
Sigma-Tau employee joined EMA since 20 11 with the exception of MrS. Marino, who was indeed the
former General Counsel at Sigma-Tau, as publicly announced by EMA w hen h e w as hi red after a ve ry
rigorous competition run by a selection panel featuring also external members from the Legal Service
of the European Commission. Prof Rasi was .D.Qj partofthat selection panel and he did .D.Qj know Mr
Marino when he was still working in industry. The statements appearing at page 17 of the Nord ie
Cochrane complaint against EMA have therefore no foundation.
We trust that the information provided in this letter has adequately addressed the points raised in your
complaint letter. Taking into account the seriousness of the accusations made via the Internet and the
echo that these allegations have had worldwide, EMA reserves the right to proteet its reputation
through all appropriate means. Piease also note that EMA will publish this reply for the sake of
transparency.
Yours sincerely,
[Signature on File]
Noel Wathion
Deputy Executive Director
CC:
Karsten J u hl Jørgensen, Deputy Di rector o f the Nordie Cochrance Centre, Rigshospitalet
Tom Jefferson, Honorary Research Fellow, Centre for Evidence Based Medicine, Oxford OX2 6GG
Margrete Auken, MEP (The Greens/Europea n Free Alliance)
Louise Brinth, PhD, MD, Danish Syncape Unit, Frederiksberg
l ~1f../ 1911 l : ·;>i; :(, Page 2/2

1 August 2016
To Carter-Ruck Solicitors
you have sent me two emails, on 8 and 21 July, and wrote in the one from 21 July:
July and August are holiday season. This is my first work day after 4 weeks holidays in July, so I have not had
any chance of reacting to your emails before today, as I have not seen them.
We shall respond as soon as we can.
bw
Peter Gøtzsche

12 August 2016
Dear Carter-Ruck solicitors,
In your letter from 8 July, you write that “Despite the gravity of those allegations [about conflicts of
interest], the EMA has not received so much as an acknowledgement of Mr Wathion's letter, let alone any
substantive response or suitable retraction and correction.”
The reason why we did not respond to this particular letter is that we raised several other conflicts of
interest issues than those related to your client, Professor Guido Rasi, and we therefore awaited the EMA’s
response to our letter in its entirety. Mr Wathion wrote to us in his letter from 17 June: “A reply to the
other issues you have raised in your complaint letter is being finalised and will be provided to you within
the next few days.” We therefore preferred to wait a few days before we responded in toto. As it turned
out, however, the EMA’s response was not sent in a “few days”, but in July when I was on holiday, so I had
no opportunity of responding.
You also write that Rasi hopes that we will agree “to amend the relevant passages of the Publication, and to
publish (in terms to be agreed) a suitable statement of correction and apology withdrawing these false
allegations.”
As researchers, we believe it would be wrong to change published documents. If errors are detected in
scientific papers, the papers are not changed but errata are published separately. We have therefore
written a separate document, which we will publish on the Nordic Cochrane Centre’s website, alongside
our complaint to the EMA from 26 May.
We hope we have thereby met the wishes of Prof. Rasi. See our corrections attached.
bw
Peter C Gøtzsche
on behalf of all authors

Trusted evidence. Informed decisions. Better health.
Nordic Cochrane Centre
Rigshospitalet, Dept. 7811
Blegdamsvej 9
2100 Copenhagen Ø, Denmark
Tel: +45 35 45 71 12
Fax: +45 35 45 70 07
E-mail: general@cochrane.dk
12 August 2016
Corrections of conflicts of interest issues in our
“Complaint to the European Medicines Agency (EMA) over maladministration at the EMA” from 26
May 2016.
We have been made aware that we have misinterpreted some of the information that was available
to us in relation to conflicts of interest issues and we therefore make corrections here.
About the EMAs executive director, we wrote:
“We noticed a Guido Rasi’s name associated with patents for inventions and wonder whether this is
the same person who is the EMA’s director. If so, we believe Rasi has failed to declare his conflicts of
interest.”
“a Guido Rasi, which we assume is the same person, holds a number of patents, some of which were
filed or approved in 2012 or 2013, and where the applicant was a drug company (Applicant: SciClone
Pharmaceuticals, Inc.; Inventors: Guido Rasi, Enrico Garaci, Francesco Bistoni, Luigina Romani, Paolo
Di Francesco) (15). As they go back less than five years, we believe he should have declared them,
according to the EMA’s regulations concerning the handling of declared interests of its employees
(16).”
“the EMA’s director, Guido Rasi, has brought in a number of people from the drug company Sigma
Tau that include Stefano Marino, his head of legal affairs. Rasi has worked with this company for
many years and apparently owns several patents together with the company (15).”
“the EMA’s director, Guido Rasi, declared on 20 July 2015 that he had no conflicts of interest (14). On
a form called ‘EMA Public Declaration of Interests,’ he replied ‘none’ to all four questions, also to
question 4, which is: ‘Other interests or facts whether or not related to the pharmaceutical industry 4
which you consider should be made known to the Agency and the public, including matter relating to
members of your household 5 .’”
The EMAs deputy executive director, Noël Wathion, has informed us that:
“EMA staff members are required to declare in their declaration of interests (DoI) any ownership of a
patent held for a period of 5 years prior to the start of employment with the Agency.”
“the inventor mentioned on a patent is the creator of the invention and is always entitled to be
designated on the patent, regardless of who files the patent application or owns the patent. An
inventor remains an inventor throughout the term of a patent, but he is not necessarily the owner of
the patent, e.g. the ownership rights may be vested originally upon, or subsequently assigned to, a
1

subject other than the inventor/s. Only the owner of a patent can enjoy economic rights with regard
to that particular invention. Therefore, neither the applicable rules, nor considerations of common
sense oblige EMA staff to declare in their DoI any patents for which they are the inventor/s, but not
the owner/s, unless the inventor is entitled to financial benefits (e.g. lump-sum or royalties)
stemming from the exploitation of the invention.”
“The Agency’s Executive Director Prof Rasi is indeed mentioned on a number of patents, even
beyond those referred to in footnote 15 of your complaint letter, but only as inventor, not as owner
of the patents. Prof Rasi does not own any patent together with Sigma-Tau. He is named as inventor
on 2 patent families for which Sigma-Tau is named as applicant or patentee. He is not even the
beneficiary of those patent families. Hence there was and there is no obligation for him to declare
these patents in his DoI as EMA staff member in accordance with EMA’s proceedings on the handling
of DoIs.”
“We would also like to clarify that Prof Rasi has never worked with or for Sigma-Tau and that no
former Sigma-Tau employee joined EMA since 2011 with the exception of Mr S. Marino, who was
indeed the former General Counsel at Sigma-Tau, as publicly announced by EMA when he was hired
after a very rigorous competition run by a selection panel featuring also external members from the
Legal Service of the European Commission. Prof Rasi was not part of that selection panel and he did
not know Mr Marino when he was still working in industry. The statements appearing at page 17 of
the Nordic Cochrane complaint against EMA have therefore no foundation.”
Our comment:
We apologize for the mistakes. We were not aware of the legal subtleties and assumed that an
inventor of a patented technology is also an owner of that patent, as it is highly unusual that
inventors give away their patents to drug companies without benefiting from them and without
having any working relationship with that particular company.
As concerns the employment of people, there are legal procedures to follow, but it is also very
common that the employer contacts people informally, encouraging them to apply for the post.
About the EMA’s rapporteur, we wrote:
”We also believe that the rapporteur for the EMA’s report, Julie Williams (2), has failed to declare
her conflicts of interest.”
We apologize for this mistake, which stems from the limited information that was available to us. In
the material from the EMA that we had acquired, we could not see where this person worked and
therefore looked her up on the Internet. Unfortunately, we found the wrong person, another
Professor Julie Williams. Therefore, what we wrote about Julie Williams in our complaint to the EMA
should be disregarded, apart from this sentence, which is correct:
“in Williams’ ‘Public declaration of interests’ on the EMA’s homepage from 21 November 2015 (13),
no conflicts of interest are declared.”
2

Sincerely,
Peter C Gøtzsche, DrMedSci, MSc
Director of the Nordic Cochrane Centre, Rigshospitalet
Professor, University of Copenhagen
Co-signatures:
Karsten Juhl Jørgensen, Deputy Director of the Nordic Cochrane Centre, Rigshospitalet
Tom Jefferson, Honorary Research Fellow, Centre for Evidence Based Medicine, Oxford OX2 6GG,
United Kingdom
Margrete Auken, MEP (The Greens/European Free Alliance)
Louise Brinth, PhD, MD, Danish Syncope Unit, Frederiksberg
3

Direct Email: adam.tudor@carter-ruck.com
Direct Fax: 020 7353 5553
Our Ref: AT/MP/1 6091.1
Your Ref: EMN408257/2016
18 August 2016
BY EMAIL & POST pcg@cochrane.dk
PRIVATE AND CONFIDENTIAL
Professor Peter C. Gøtzsche
Nordie Cochrane Centre
Rigshospitalet, Dept. 7811
Blegsdamsvej 9
2100 Capenhagen Ø,
Denmark
Carter-Rucl<
Dear Sir
Our Client: Professor Guido Rasi
We refer to your email dated 12 August.
Our client is prepared to accept your proposal of a separate errata document, to be
published on the Nordie Cochrane Centre' s website, alongside your original
complaint to the EMA from 26 May.
The current wording of the document is however not acceptable to our client. We
enclose a revised version, in which our amendments are highlighted, which we trust
is uncontroversial.
Carter- Ru c k Soliciters
6 S t Andrew Street
London EC4A 3AE
T 020 7353 5005
F 020 7353 5553
DX 333 Chancery Lane
www.carter-ruckcom
Piease confirm this version of the wording is now agreed, and that the errata
document will be published online by no later than close of businesson Friday 26
August.
We look forward to hearing from you.
Yours faithfully
&k! ~~
Carter-Ruck
Partners
Alasdair Pepper
Guy Martin
Nigei Tait
Ruth Collard
Cameron Doley
Claire Gill
Adam Tudor
Isabel Martoreli
Partnershi p Secretary
Helen Burrluck
PCRI-2 1455171
Authorised and regulated
by the Solleotors Regulat1on
Authority
SRA No. 44769

Q)
Cochrane
Nordie
Trusted evidence. lnformed decisions. Better health.
Nordie Cochrane Centre
Rigshospitalet, Dept. 7811
Blegdamsvej 9
2100 Capen hagen Ø, Denmark
Tel: +45 35 45 7112
Fax: +45 35 45 70 07
E-mai l: genera l@cochrane.dk
12 August 2016
Cerreetions of conflicts of interest issues in our
" Complaint to the European Medieines Agenev (EMA) over maladministration at the EMA" from 26
May 2016.
W e have been made aware that we have misinterpreted som e of the information t hat was available
to us in relation to conflicts of interest issues and we therefore make corrections here.
About the E MAs executive director, we wrote:
"We noticed a Guido Rasi's name associated with patents forinventionsand wonder whether this is
the same person who is the EMA's di rector. lf so, we believe Rasi has fa iled to declare his conflicts of
interest."
"a Guido Rasi, which we assume is the same person, holds a number of patents, some of which were
filed or approved in 2012 or 2013, and where the applicant was a drug company (Applicant: SciCione
Pharmaceuticals, Ine.; Inventars: Guido Rasi, Enrico Garaci, Francesco Bistoni, Luigina Romani, Paolo
Di Francesco) (15). As they go back less than five years, we believe he should have declared them,
according to the EMA's regulations concerning the handling of declared interests of its employees
(16)."
"the EMA's director, Guido Ras i, has brought in a number of people fromthedrug company Sigma
Tau that inelude Stefano Marino, his head of legal affairs. Rasi has worked with this company for
many years and apparently owns several patents together with the company (15)."
"the EMA's di rector, Guido Rasi, declared on 20 J u ly 2015 that he had no conflicts of int erest (14). O n
a form called 'EMA Public Declaration of lnterests,' he replied 'none' to all four questions, also to
question 4, which is: 'Other interests or facts whether or not related to the pharmaceutical industry 4
which you consider should be made known to the Agency and the public, i nduding matter relating to
members of your house hold 5 ."'
The E MAs deputy executive di rector, Noel Wathion, has informed us that:
"EMA staff members a re required to declare in their declaration of interests (Do l) a ny ownership of a
patent held for a period of S yea rs prior tothestart of employment with the Agency."
"the inventar mentianed o n a patent is the creator of the invention and is always entitled to be
designated o n the patent, regardless of who files the patent application or owns t he patent. An
inventar remains a n inventor throughout the term of a patent, but h e is not necessarily the owner o f
the patent, e.g. the ownership rights may be vested originally upon, or su bsequently assigned t o, a

subject other than the inventar/s. Only the owner of a patent can en joy economic rights with regard
to t hat particular invention. Therefore, neither the applicable rules, nor considerations of common
sense oblige EMA staff to declare in their Dol a ny patents for which they a re the inventar/s, but not
the owner/s, unless the inventar isentitled to financial benefits (e.g. lump-sum or royalties)
stemming from the exploitation of the invention."
"The Agency's Executive Director Prof Rasi is indeed mentianedon a number of patents, even
beyond t hose referred to in footnote 15 of your complaint letter, but o n ly as inventar, not as owner
ofthe patents. Prof Rasi does not own anypatent together with Sigma-Tau. He is narned as inventar
on 2 patent families for which Sigma-Tau is narned as applicant or patentee. He is noteven t he
beneficiary ofthose patent families. Hence there was and there is no obligation for him to declare
these patents in his Dol as EMA staff member in accordance with EMA's proceedings on the handling
of Dals."
"W e would also like to clarify t hat Prof Ras i has never worked with o r for Sigma-Tau and t hat no
former Sigma-Tau employee joined EMA since 2011 with the exception of M r S. Marino, who was
indeed the former General Counsel at Sigma-Tau, as publicly announced by EMA when he was hi red
after a very rigorous competition run by a selection panel featuring also external members from the
Legal Service of the European Commission. Prof Ras i was not partofthat selection panel and h e did
not know M r Marino when he was still working in industry. The statements appearing at page 17 of
the Nordie Cochrane complaint aga inst EMA have therefore no foundation."
Our comment:
We apologize to Professor Rasi and Stefano Marino for our tÅe mistakes.
W e were not aware of the legal subtleties and assumed that an inventar of a patented technology is
also an owner of that patent. Professor Rasi has explained to us, and we accept, that t his is not
correct in his case. , as it is l:ligl:ll•t unusual that inventars give away their ~atents to El rug com~anies
without 8enefiting from tl:lem ane without having a ny •,vorking relations Ri~ witl:l tl:lat ~articular
com13any.
As concerns the employment of people, EMA has confirmed, and we accept, that Professor Rasi did
not bring anyane to EMA from Sigma-Tau. We acknowledge that Stefano Marino worked previously
at Sigma-Tau, but w as recruited according to the ordinary, rigorous EU selection procedures and
received no favourable treatment at all. there a re legal f3FoceEIYres to tollow, eut it is also very
common that t he em~ l oyer contacts ~eo~ l e informally, encouraging tl=lern to a~~ ly for tl:le ~ost.
About the EMA's rapporteur, we wrote:
"We also believe that the rapporteur for the EMA's re port, Julie Williams (2), has failed to declare
her conflicts of interest."
W e apologize to Doctor Julie Williams and EMA for this mistake, which stems from the limited
info rmation that was avai lable to us. In the material from the EMA that we had acquired, we could
not see where this person worked and therefore loaked her up on the Internet. Unfortunately, we
2

found the wrong person, a nother Professor Julie Williams. Therefore, w hat we wrote about Julie
Williams in our complaint to the EMA should be disregarded, a part from t his sentence, which is
correct:
"in Williams' 'Public declaration of interests' on the EMA's homepage from 21 November 2015 (13),
no conflicts of interest a re declared."
Sincerely,
Peter C Gøtzsche, DrMedSci, MSc
Di rector of the Nordie Cochrane Centre, Rigshospitalet
Professor, University of Copenhagen
Co-signatu res:
Karsten J u hl Jørgensen, Deputy Di rector of the Nordie Cochrane Centre, Rigshospitalet
Tom Jefferson, Honorary Research Fellow, Centre for Evidence Based Medicine, Oxford OX2 6GG,
United Kingdom
Margrete Auken, MEP (The Greens/European Free Alliance)
Louise Brinth, PhD, MD, Danish Syncape Unit, Frederiksberg
3

23 August 2016
We enclose our comments to your letter from 18 August where we suggest a compromise, which we trust
is uncontroversial.
bw
Peter Gøtzsche on behalf of all authors

Trusted evidence. Informed decisions. Better health.
Nordic Cochrane Centre
Rigshospitalet, Dept. 7811
Blegdamsvej 9
2100 Copenhagen Ø, Denmark
Tel: +45 35 45 71 12
Fax: +45 35 45 70 07
E-mail: general@cochrane.dk
23 August 2016
Corrections of conflicts of interest issues in our
“Complaint to the European Medicines Agency (EMA) over maladministration at the EMA” from 26
May 2016.
Referring to your letter from 18 August, we are pleased that your client accepts that we publish a
separate errata document on the Nordic Cochrane Centre' s website, alongside our original
complaint to the EMA from 26 May.
You say that the current wording of the document is not acceptable to your client and you have sent
suggested amendments, which you ask us to accept.
You highlighted in our document your suggested amendments in red and by using overstrike. The
first paragraph just below, which is included in our suggested correction document, was sent to us
by the EMAs deputy executive director, Noël Wathion:
“We would also like to clarify that Prof Rasi has never worked with or for Sigma-Tau and that no former
Sigma-Tau employee joined EMA since 2011 with the exception of Mr S. Marino, who was indeed the former
General Counsel at Sigma-Tau, as publicly announced by EMA when he was hired after a very rigorous
competition run by a selection panel featuring also external members from the Legal Service of the European
Commission. Prof Rasi was not part of that selection panel and he did not know Mr Marino when he was still
working in industry. The statements appearing at page 17 of the Nordic Cochrane complaint against EMA have
therefore no foundation.”
We apologize to Professor Rasi and Stefano Marino for our the mistakes.
We were not aware of the legal subtleties and assumed that an inventor of a patented technology is also an
owner of that patent. Professor Rasi has explained to us, and we accept, that this is not correct in his case. ,
as it is highly unusual that inventors give away their patents to drug companies without benefiting from them
and without having any working relationship with that particular company.
As concerns the employment of people, EMA has confirmed, and we accept, that Professor Rasi did not bring
anyone to EMA from Sigma-Tau. We acknowledge that Stefano Marino worked previously at Sigma-Tau, but
was recruited according to the ordinary, rigorous EU selection procedures and received no favourable
treatment at all. there are legal procedures to follow, but it is also very common that the employer contacts
people informally, encouraging them to apply for the post.
About the EMA’s rapporteur, we wrote:
”We also believe that the rapporteur for the EMA’s report, Julie Williams (2), has failed to declare her conflicts
of interest.”
We apologize to Doctor Julie Williams and EMA for this mistake
1

Our comments to your suggested amendments
An apology is a very personal thing, and in our opinion the person asking for an apology should not
require a particular text or format, as the apology would then not be genuine. We are prepared,
however, to take your suggested amendments into consideration.
As it was already clear in our document to whom we address our apologies, there is no need to
mention the names again. It is also clear from your own text, which we inserted just above our
apologies, what the apologies are about and there is therefore no need to repeat this as part of our
apologies. However, to accommodate your wishes, we are willing to do this.
We need to protect our own reputations and therefore need to explain to the readers of this
document that our mistakes were made in good faith. Therefore, we cannot accept that you deleted
our explanations. We furthermore believe that these explanations are helpful for the readers of this
document and therefore have general public interest, and we wish to note that both the EMA and
ourselves serve the public interest. Finally, please take into account that four of us are scientists and
the fifth is a politician. Being scientists or politicians, we can write what others have told us, making
it clear that this is so, but we cannot allow ourselves to be forced to accept statements as fact when
we have had no possibility of checking these facts ourselves.
For these reasons, we suggest this compromise, which we trust is uncontroversial:
We apologize for our mistakes.
We were not aware of the legal subtleties and assumed that an inventor of a patented technology is
also an owner of that patent, as it is highly unusual that inventors give away their patents to drug
companies without benefiting from them and without having any working relationship with that
particular company. Noel Wathion has explained to us that Professor Rasi is not the owner of the
patents for which he is named as inventor.
As concerns the employment of people, there are legal procedures to follow, but it is also very
common that the employer contacts people informally, encouraging them to apply for the post. The
EMA has stated to us that Professor Rasi did not bring anyone to EMA from Sigma-Tau and that
Stefano Marino was recruited according to the ordinary, rigorous EU selection procedures and
received no favourable treatment at all.
About the EMA’s rapporteur, we wrote:
”We also believe that the rapporteur for the EMA’s report, Julie Williams (2), has failed to declare
her conflicts of interest.”
We apologize for this mistake
2

Sincerely,
Peter C Gøtzsche, DrMedSci, MSc
Director of the Nordic Cochrane Centre, Rigshospitalet
Professor, University of Copenhagen
Co-signatures:
Karsten Juhl Jørgensen, Deputy Director of the Nordic Cochrane Centre, Rigshospitalet
Tom Jefferson, Honorary Research Fellow, Centre for Evidence Based Medicine, Oxford OX2 6GG,
United Kingdom
Margrete Auken, MEP (The Greens/European Free Alliance)
Louise Brinth, PhD, MD, Danish Syncope Unit, Frederiksberg
3

At 12:40 24-08-2016, Helena Shipman wrote:
Dear Sir,
We refer to your email below and its attachment.
Our client considers that that the wording of the errata document is most of the way there, albeit it is still
not acceptable in its current form. Rather that engage in further protracted correspondence, we propose a
telephone discussion to try to resolve any remaining issues. Please confirm if you are amenable to this
approach, and if so please let us know when would be convenient.
We look forward to hearing from you.
Yours faithfully,
Carter-Ruck
Carter-Ruck Solicitors
---
Our reply:
27 August 2016
Dear lawyers
We prefer to communicate in writing.
bw
Peter Gøtzsche
Margrete Auken
Louise Brinth
Tom Jefferson
Karsten Juhl Jørgensen

Direct Email: adam.tudor@carter-ruck.com
Direct Fax: 020 7353 5553
Our Ref: AT/MP/ 16091 .1
Your Ref: EMA/408257/20 16
7 September 2016
BY EMAIL & POST pcg @cochrane.dk
PRIVATE AND CONFIDENTIAL
Professor Peter C. Gøtzsche
Nordie Cochrane Centre
Rigshospitalet, Dept. 7811
Blegsdamsvej 9
21 00 Capenhagen Ø,
Denmark
Carter-Rucl<
Dear Sir
Our Client: Professor Guido Rasi
We refer to our previous correspondence in this matter and, most recently, to your
emailed letter dated 23 August 2016.
As we observed in our email of 24 August, we are hopeful that the parties are now
not far apart.
W e set out below our proposed amendments to those contained in your 23 August
proposal. You will see that, for your ease of reference, we have shown your
amendments in red , and our proposed further changes underlined in black or struck
through.
Carte r - Ruck Soliciters
6 S t Andrew Street
London EC4A 3AE
T 020 7353 5005
F 020 7353 5553
ox 333 Chancery Lane
wwwcarter-ruck.com
W e apologize to Professor Rasi and Stefano Marino for our mistakes.
We were not aware of the legal subtleties and assumed that an
inventar of a patented technology is also an owner of that patent, as it
is ~ unusual that inventars give away their patents to drug
companies without benefiting from them and without having any
working relationship with that particular company. Noel Wathion has
explained to us that Professor Rasi is not the owner of the patents for
which he is narned as inventar. On the basis of these assurances we
accept that Professor Rasi has never had, and does not have. any
economic riqhts or financial interest or benetit (whether actual or
potential) in, or arising from. any of the patents to which the Publication
refers.
As concerns the employment of people, there are legal procedures to
follow, but i t is al so VBfY common that the employer contacts people
informally, encouraging them to apply for the post. However. the EMA
has stated to us, and as such we accept, that Professor Rasi did not
bring anyone to EMA from Sigma-Tau and that Stefano Marino was
recruited according to the ordinary, rigorous EU selection procedures
and received no tavaurable treatment at all.
W e comment as follows:
First, you will note that we have amended to name Professor Rasi and Mr
Marino. This is important to our clients and, we believe, entirely reasonable given the
personal allegations made against both individuals. In the body of your letter of 23
August (page 2, paragraph 2) you in faet confirmed that you were wil ling to do this
PCRI -2 156421 . 1
Partners
Alasdair Pepper
Guy Martin
Nigellait
Ruth Coltard
Cameron Doley
Claire Gill
Adam Tuder
Isabel Martoneli
Partnership Secretary
Helen Burrluck
Authorised and regulated
by the Sol,citors Regulation
Authonty
SRA No. 44769

ut (no doubt inadvertently) omitted it from the amendments, so we trust this will be
uncontroversial.
Secondly, while our client is willing to accept your proposal for the paragraph
commencing "We were not aware', it is essential that this paragraph goes on to make
clear that, in consequence, our client has never had any financial benetit Again, this
should be uncontroversial.
You will note that our proposais for the second and third paragraphs below confirm
Nordie Cochrane's acceptance of the position as explained to you. In your 23 August
letter you state that you "cannot allow [y]ourselves to be forced to accept statements
of faet when [you] have no possibility of checking these facts ourselves'. Leaving
aside for a moment the faet that the authors of the effending publication felt able to
make these untrue statements of faet in the first place without any proper verification,
it is clearly essential, and equitable, that in order to properly correct the record, the
statement makes clear Nordie Cochrane's acknowledgment of the true position (or
else readers will be likely to consider our clients' statements to be self-serving and
therefore not credible). We would hope that, given the assurances provided by both
EMA and Professor Rasi and the factual explanation given by us in our capacity as
Professor Rasi's solicitors, Nordie Cochrane will, on reflection, be willing to accept
those explanations and to make that clear in the statement.
W e look forward to hearing from you and hopematters can be resolved without delay.
Yours faithfully
G-/ru~~
Carter-Ruck
Carter- Ru c k
PCRI-2156421 l 2

11 September 2016
To Carter-Ruck solicitors
We agree that we are now not far apart.
You have deleted the words “highly” and “very” in your suggested amendment although these words are
appropriate. It is not only highly unusual, it is in fact extremely unusual, that inventors give away their
patents to a particular drug company - in this case Sigma-Tau - without benefiting from them and without
having any working relationship with that particular company. We had never heard of any such cases
before but are now told that this is the case for Guido Rasi. Similarly, it is very common that the employer
contacts people informally, encouraging them to apply for a vacant post, particularly if that post is
important for the institution, and we can see nothing wrong with that. This has nothing to do with
nepotism, provided all applicants are treated equally in the subsequent selection procedure. However,
since you wish to delete these two words, we will accept this proposal.
We wrote to you, on 23 August: “As it was already clear in our document to whom we address our
apologies, there is no need to mention the names again. It is also clear from your own text, which we
inserted just above our apologies, what the apologies are about and there is therefore no need to repeat
this as part of our apologies. However, to accommodate your wishes, we are willing to do this.”
Thus, we said that we were willing to repeat what the apologies were about, and we also inserted this in
the text. In your letter from 7 September, you indicate that we should have said that we were willing to
mention the names again, but this was not what we meant and wrote. Allow us to say again that an
apology is a very personal thing, and that, in our opinion, the person asking for an apology should not
require a particular text or format, as the apology would then not be genuine.
As we have already explained, being scientists or politicians, we can write what others have told us, making
it clear that this is what they told us, but we cannot allow ourselves to be forced to accept such statements
as fact when we have had no possibility of checking these facts ourselves. As lawyers, you know very well
that in court cases, one cannot force people to accept and declare that what others tell them is the truth.
Therefore, we cannot accept the following amendments, which you suggested in your letter:
“On the basis of these assurances we accept that Professor Rasi has never had, and does not have, any
economic rights or financial interest or benefit (whether actual or potential) in, or arising from, any of the
patents to which the Publication refers” and “and as such we accept.”
We accepted to take your suggested amendments into consideration, and we believe we have been very
forthcoming in changing the text according to your wishes.
best wishes
Peter Gøtzsche
Margrete Auken
Louise Brinth
Tom Jefferson
Karsten Juhl Jørgensen

Direct Email: adam .tudor@carter-ruck.com
Direct Fax: 02 0 7353 5553
Our Ref: AT/MP/16091.1
Your Ref: EMA/408257/20 16
16 September 2016
BY EMAIL & POST pcg@cochrane.dk
PRIVATE AND CONFIDENTIAL
Professor Peter C. Gøtzsche
Nordie Cochrane Centre
Rigshospitalet, Dept. 7811
Blegsdamsvej 9
2100 Capenhagen
Denmark
Carter-Rucl<
Dear Sir
Our Client: Professor Guido Rasi
We refer to your email dated 11 September 2016.
We note your agreement to the removal of the words "highly" and "very" from the
apology. ·
Your position on identifying our client and Mr Marino in your email dated 23 August
was actually very clear and beyond any possible misunderstanding. Given that you
have agreed to name Doctor Julie Williams and EMA in your proposed wording, we
trust that you will accord our client and Mr Marino the same treatment. We are not
asking a particular text or format of the apology. We certainly welcome your
statement that the apology is a personal thing and in faet we are only asking that you
simply name the persons to whom the apology is addressed.
Carter· Ruck Soliciters
6 S t Andrew Street
London EC4A 3AE
T 020 7353 5005
F 020 7353 5553
DX 333 Chancery Lane
www.carter-ruck.com
In light of your reluctance to accept our client's assurances and explanations, we
propose that they are instead , at the very least, acknowledged. We have therefore
set out below a further arnendment to what we believe is the final wording of the
apology, which we trust should be uncontroversial:
We apologise to Professor Rasi and Stefano Marino for our mistakes.
PCRI-2161614.1
We were not aware of the legal subtleties and assumed that an
inventar of a patented technology is also an owner of that patent, as it
is unusual that inventars give away their patents to drug companies
without benefiting from them and without having any working
relationship with that particular company. Noel Wathion has explained
to us that Professor Rasi is not the owner of the patents for which he is
narned as inventar. We acknowledge Mr Wathion's statement that
Professor Rasi has never had. and does not have. any economic rights
or financial interest or benetit (whether actual or potential) in. or arising
from . a ny of the patents to which the Publication refers.
As concerns the employment of people, there are legal procedures to
follow, but it is also common that the employer contacts people
informally, encouraging them to apply for the post. However, the EMA
has stated to us that Professor Rasi did not bring anyane to EMA from
Sigma-Tau and that Stefano Marino was recru ited according to the
Partners
Alasdair Pepper
Guy Martin
Nigellait
Ruth Collard
Cameron Doley
Claire Gill
AdamTuder
Isabel Martoreli
Partnership Secretary
Helen Burrluck
Authorised and r·egulated
by the Solicitars Regulation
Authority
SRA No. 44769

Carter-Ru c k
ordinary, rigorous EU selection procedures and received no favourable
treatment at all.
[And]
We apologize to Doctor Julie Williams and EMA forthis mistake, which
stems from the limited information that was available to us. In the
material from the EMA that we had acquired, we could not see where
this person worked and therefore looked her up on the Internet.
Unfortunately, we found the wrong person, another Professor Julie
Williams. Therefore, what we wrote about Julie Williams in our
complaint to the EMA should be disregarded, apart from this sentence,
which is correct:
"in Williams' 'Public dec/aration of interests' on the EMA 's homepage
from 21 November 2015 (13), no conflicts of interest are declared."
We look forward to hearing from you and hope this matter can now finally be resolved .
Yours faithfully
~ -~
Carter-Ruck
PCRI -2161614.1 2

26 September 2016
To Carter-Ruck solicitors
Referring to our letter from 11 September, you say that our position on identifying Guido Rasi and Stefano
Marino in your email dated 23 August was actually very clear and beyond any possible misunderstanding.
We believe we know best what our position is but apologize if we were not sufficiently clear about this.
We do not agree that we treat people differently, as we mention all three names in our apology.
You state: “In light of your reluctance to accept our client's assurances and explanations, we propose that
they are instead, at the very least, acknowledged. We have therefore set out below a further amendment
to what we believe is the final wording of the apology, which we trust should be uncontroversial.” Your
suggested amendment is the underlined sentence:
Noel Wathion has explained to us that Professor Rasi is not the owner of the patents for which he is named
as inventor. We acknowledge Mr Wathion's statement that Professor Rasi has never had. and does not
have any economic rights or financial interest or benefit (whether actual or potential) in, or arising from,
any of the patents to which the Publication refers.
Firstly, your suggested amendment misses the context. Secondly, Wathion has never made any such
statement to us; this statement was made by Rasi’s lawyers, Carter-Ruck solicitors. Thirdly, the amendment
is not necessary, as we had already previously acknowledged Wathion’s explanations:
“We were not aware of the legal subtleties and assumed that an inventor of a patented technology is also
an owner of that patent, as it is highly [you asked us to delete “highly”, which we accepted to do] unusual
that inventors give away their patents to drug companies without benefiting from them and without having
any working relationship with that particular company. Noel Wathion has explained to us that Professor
Rasi is not the owner of the patents for which he is named as inventor.”
We accepted to take your suggested amendments into consideration, and we believe we have been very
forthcoming in changing the text according to your wishes.
Sincerely,
Peter C Gøtzsche, DrMedSci, MSc
Director of the Nordic Cochrane Centre, Rigshospitalet
Professor, University of Copenhagen
Co-signatures:
Karsten Juhl Jørgensen, Deputy Director of the Nordic Cochrane Centre, Rigshospitalet
Tom Jefferson, Honorary Research Fellow, Centre for Evidence Based Medicine, Oxford, UK
Margrete Auken, MEP (The Greens/European Free Alliance)
Louise Brinth, PhD, MD, Danish Syncope Unit, Frederiksberg

Date: Fri, 30 Sep 2016 14:36:25 +0000
From: Helena Shipman
To: '"Peter C. Gtzsche"'
CC: "jefferson.tom@gmail.com" ,
"Margrete.Auken@ft.dk" ,
"margrete.auken@europarl.europa.eu" ,
"louisebrinth@live.dk" , "kj@cochrane.dk"
, Debbie McLaren-Smith
, Adam Tudor
Subject: RE: Guido Rasi [CR-PCR1.FID114015]
Dear Sirs,
We refer to your email below.
Our client is prepared to accept your proposed wording of the apology, as it is imperative that the public is
alerted as to the true state of matters, and in addition he has no desire to engage further in protracted
correspondence and mutual inconvenience. For the avoidance of doubt, the agreed wording for the
apology is as follows:
We apologize for our mistakes.
We were not aware of the legal subtleties and assumed that an inventor of a patented technology is also an
owner of that patent, as it is unusual that inventors give away their patents to drug companies without
benefiting from them and without having any working relationship with that particular company. Noel
Wathion has explained to us that Professor Rasi is not the owner of the patents for which he is named as
inventor.
As concerns the employment of people, there are legal procedures to follow, but it is also common that the
employer contacts people informally, encouraging them to apply for the post. The EMA has stated to us
that Professor Rasi did not bring anyone to EMA from Sigma-Tau and that Stefano Marino was recruited
according to the ordinary, rigorous EU selection procedures and received no favourable treatment at all.
[And]
We apologize to Doctor Julie Williams and EMA for this mistake, which stems from the limited information
that was available to us. In the material from the EMA that we had acquired, we could not see where this
person worked and therefore looked her up on the Internet. Unfortunately, we found the wrong person,
another Professor Julie Williams. Therefore, what we wrote about Julie Williams in our complaint to the
EMA should be disregarded, apart from this sentence, which is correct:
in Williams Public declaration of interests on the EMAs homepage from 21 November 2015 (13), no conflicts
of interest are declared.
Please confirm that the above apology will be published on the Nordic Cochrane website by no later than
close of business on Wednesday 5 October 2016.
We look forward to hearing from you.

Yours faithfully,
Carter-Ruck
Helena Shipman
Solicitor, Carter-Ruck
helena.shipman@carter-ruck.com
Carter-Ruck Solicitors
6 St Andrew Street
London EC4A 3AE
T 020 7353 5005
F 020 7353 5553
DX 333 Chancery Lane
www.carter-ruck.com
One of the UK's best-known law firms, Carter-Ruck has a longstanding reputation for its expertise in the
field of litigation and dispute resolution.
Home | Media Law | International | Commercial Disputes | News
Carter-Ruck is a CarbonNeutral® company. Think of the environment. Do you need to print this email?
From: "Peter C. Gøtzsche" [mailto:pcg@cochrane.dk]
Sent: 27 September 2016 12:13
To: Helena Shipman
Cc: jefferson.tom@gmail.com; Margrete.Auken@ft.dk; margrete.auken@europarl.europa.eu;
louisebrinth@live.dk; kj@cochrane.dk; Debbie McLaren-Smith; Adam Tudor
Subject: Re: Guido Rasi
26 September 2016
To Carter-Ruck solicitors
Referring to our letter from 11 September, you say that our position on identifying Guido Rasi and Stefano
Marino in your email dated 23 August was actually very clear and beyond any possible misunderstanding.
We believe we know best what our position is but apologize if we were not sufficiently clear about this.
We do not agree that we treat people differently, as we mention all three names in our apology.
You state: In light of your reluctance to accept our client's assurances and explanations, we propose that
they are instead, at the very least, acknowledged. We have therefore set out below a further amendment
to what we believe is the final wording of the apology, which we trust should be uncontroversial. Your
suggested amendment is the underlined sentence:
Noel Wathion has explained to us that Professor Rasi is not the owner of the patents for which he is named
as inventor. We acknowledge Mr Wathion's statement that Professor Rasi has never had. and does not
have any economic rights or financial interest or benefit (whether actual or potential) in, or arising from,
any of the patents to which the Publication refers.
Firstly, your suggested amendment misses the context. Secondly, Wathion has never made any such

statement to us; this statement was made by Rasis lawyers, Carter-Ruck solicitors. Thirdly, the amendment
is not necessary, as we had already previously acknowledged Wathions explanations:
We were not aware of the legal subtleties and assumed that an inventor of a patented technology is also an
owner of that patent, as it is highly [you asked us to delete highly, which we accepted to do] unusual that
inventors give away their patents to drug companies without benefiting from them and without having any
working relationship with that particular company. Noel Wathion has explained to us that Professor Rasi is
not the owner of the patents for which he is named as inventor.
We accepted to take your suggested amendments into consideration, and we believe we have been very
forthcoming in changing the text according to your wishes.
Sincerely,
Peter C Gøtzsche, DrMedSci, MSc
Director of the Nordic Cochrane Centre, Rigshospitalet
Professor, University of Copenhagen
Co-signatures:
Karsten Juhl Jørgensen, Deputy Director of the Nordic Cochrane Centre, Rigshospitalet
Tom Jefferson, Honorary Research Fellow, Centre for Evidence Based Medicine, Oxford, UK
Margrete Auken, MEP (The Greens/European Free Alliance)
Louise Brinth, PhD, MD, Danish Syncope Unit, Frederiksberg

From: Helena Shipman
To: '"Peter C. Gøtzsche"'
CC: "'jefferson.tom@gmail.com'" ,
"'Margrete.Auken@ft.dk'" ,
"'margrete.auken@europarl.europa.eu'" ,
"'louisebrinth@live.dk'" , "'kj@cochrane.dk'"
, Debbie McLaren-Smith
, Adam Tudor
Subject: RE: Guido Rasi [CR-PCR1.FID114015]
Date: Thu, 6 Oct 2016 17:08:22 +0000
Dear Sirs,
We refer to our email below.
Please confirm by return that you will publish forthwith the apology set out in our email, now agreed
between the parties, and in any event by no later than close of business tomorrow, Friday 7 October.
We look forward to hearing from you.
Yours faithfully,
Carter-Ruck
Helena Shipman
Solicitor, Carter-Ruck
helena.shipman@carter-ruck.com
Carter-Ruck Solicitors
6 St Andrew Street
London EC4A 3AE
T 020 7353 5005
F 020 7353 5553
DX 333 Chancery Lane
www.carter-ruck.com
One of the UK's best-known law firms, Carter-Ruck has a longstanding reputation for its expertise in the
field of litigation and dispute resolution.
Home | Media Law | International | Commercial Disputes | News

7 October 2016
Dear Helena Shipman,
We will upload our apology on the Nordic Cochrane Centre's website under
http://nordic.cochrane.org/research-highlights on Monday 10 October.
yours sincerely
Peter C Gøtzsche, DrMedSci, MSc, Director and Professor, the Nordic Cochrane Centre
Karsten Juhl Jørgensen, MD, DrMedSci, Deputy Director, the Nordic Cochrane Centre
Tom Jefferson, MD, Honorary Research Fellow, Centre for Evidence Based Medicine, Oxford, UK
Margrete Auken, MEP (The Greens/European Free Alliance)
Louise Brinth, MD, PhD, Danish Syncope Unit, Frederiksberg

Trusted evidence. Informed decisions. Better health.
Nordic Cochrane Centre
Rigshospitalet, Dept. 7811
Blegdamsvej 9
2100 Copenhagen Ø, Denmark
Tel: +45 35 45 71 12
Fax: +45 35 45 70 07
E-mail: general@cochrane.dk
10 October 2016
Follow-up on our complaint to the European Medicines Agency (EMA) over maladministration at
the EMA related to safety of the HPV vaccines
On May 2016, we submitted a Complaint to the European Medicines Agency (EMA) over
maladministration at the EMA related to safety of the HPV vaccines.
The replies we received from the EMA came in three parts:
1. On 17 June, Noël Wathion, the EMA’s Deputy Executive Director, addressed conflicts of interest
issues related to the EMA’s Executive Director, Guido Rasi (2 pages).
2. On 1 July, Noël Wathion sent the EMA’s response to the other issues we had raised (17 pages).
3. Starting on 8 July and ending on 30 September, Carter-Ruck solicitors in London sent a total of 8
letters to us on behalf of their client, Guido Rasi, which we responded to.
The EMA’s replies to us did not fully address our concerns. Some of our concerns were not addressed
at all, and several of the EMA’s statements were either wrong or seriously misleading, or irrelevant
for the criticism we had posed. We have therefore today submitted a Complaint to the EU
ombudsman over maladministration at the EMA related to safety of the HPV vaccines.
The EMA has made us aware that we have misinterpreted some of the information that was
available to us in relation to conflicts of interest issues and we therefore make corrections here as
well as in our Complaint to the EU ombudsman over maladministration at the EMA related to
safety of the HPV vaccines. We have included the entire correspondence between Wathion and
Rasi’s law firm and us in an Appendix to our complaint to the ombudsman, as we believe it has
considerable public interest.
About the EMAs executive director, we wrote in our complaint to the EMA:
“We noticed a Guido Rasi’s name associated with patents for inventions and wonder whether this is
the same person who is the EMA’s director. If so, we believe Rasi has failed to declare his conflicts of
interest.”
“a Guido Rasi, which we assume is the same person, holds a number of patents, some of which were
filed or approved in 2012 or 2013, and where the applicant was a drug company (Applicant: SciClone
Pharmaceuticals, Inc.; Inventors: Guido Rasi, Enrico Garaci, Francesco Bistoni, Luigina Romani, Paolo
Di Francesco) (15). As they go back less than five years, we believe he should have declared them,
according to the EMA’s regulations concerning the handling of declared interests of its employees
(16).”
1

“the EMA’s director, Guido Rasi, has brought in a number of people from the drug company Sigma
Tau that include Stefano Marino, his head of legal affairs. Rasi has worked with this company for
many years and apparently owns several patents together with the company (15).”
“the EMA’s director, Guido Rasi, declared on 20 July 2015 that he had no conflicts of interest (14). On
a form called ‘EMA Public Declaration of Interests,’ he replied ‘none’ to all four questions, also to
question 4, which is: ‘Other interests or facts whether or not related to the pharmaceutical industry 4
which you consider should be made known to the Agency and the public, including matter relating to
members of your household 5 .’”
The EMAs deputy executive director, Noël Wathion, has informed us that:
“EMA staff members are required to declare in their declaration of interests (DoI) any ownership of a
patent held for a period of 5 years prior to the start of employment with the Agency.”
“the inventor mentioned on a patent is the creator of the invention and is always entitled to be
designated on the patent, regardless of who files the patent application or owns the patent. An
inventor remains an inventor throughout the term of a patent, but he is not necessarily the owner of
the patent, e.g. the ownership rights may be vested originally upon, or subsequently assigned to, a
subject other than the inventor/s. Only the owner of a patent can enjoy economic rights with regard
to that particular invention. Therefore, neither the applicable rules, nor considerations of common
sense oblige EMA staff to declare in their DoI any patents for which they are the inventor/s, but not
the owner/s, unless the inventor is entitled to financial benefits (e.g. lump-sum or royalties)
stemming from the exploitation of the invention.”
“The Agency’s Executive Director Prof Rasi is indeed mentioned on a number of patents, even
beyond those referred to in footnote 15 of your complaint letter, but only as inventor, not as owner
of the patents. Prof Rasi does not own any patent together with Sigma-Tau. He is named as inventor
on 2 patent families for which Sigma-Tau is named as applicant or patentee. He is not even the
beneficiary of those patent families. Hence there was and there is no obligation for him to declare
these patents in his DoI as EMA staff member in accordance with EMA’s proceedings on the handling
of DoIs.”
“We would also like to clarify that Prof Rasi has never worked with or for Sigma-Tau and that no
former Sigma-Tau employee joined EMA since 2011 with the exception of Mr S. Marino, who was
indeed the former General Counsel at Sigma-Tau, as publicly announced by EMA when he was hired
after a very rigorous competition run by a selection panel featuring also external members from the
Legal Service of the European Commission. Prof Rasi was not part of that selection panel and he did
not know Mr Marino when he was still working in industry. The statements appearing at page 17 of
the Nordic Cochrane complaint against EMA have therefore no foundation.”
We apologize for our mistakes.
We were not aware of the legal subtleties and assumed that an inventor of a patented technology is
also an owner of that patent, as it is unusual that inventors give away their patents to drug
companies without benefiting from them and without having any working relationship with that
2

particular company. Noel Wathion has explained to us that Professor Rasi is not the owner of the
patents for which he is named as inventor.
As concerns the employment of people, there are legal procedures to follow, but it is also common
that the employer contacts people informally, encouraging them to apply for the post. The EMA has
stated to us that Professor Rasi did not bring anyone to EMA from Sigma-Tau and that Stefano
Marino was recruited according to the ordinary, rigorous EU selection procedures and received no
favourable treatment at all.
About the EMA’s rapporteur, we wrote:
”We also believe that the rapporteur for the EMA’s report, Julie Williams (2), has failed to declare
her conflicts of interest.”
We apologize for this mistake, which stems from the limited information that was available to us. In
the material from the EMA that we had acquired, we could not see where this person worked and
therefore looked her up on the Internet. Unfortunately, we found the wrong person, another
Professor Julie Williams. Therefore, what we wrote about Julie Williams in our complaint to the EMA
should be disregarded, apart from this sentence, which is correct:
“in Williams’ ‘Public declaration of interests’ on the EMA’s homepage from 21 November 2015 (13),
no conflicts of interest are declared.”
Sincerely,
Peter C Gøtzsche, Professor, Director of the Nordic Cochrane Centre, Rigshospitalet, Denmark
Karsten Juhl Jørgensen, Deputy Director of the Nordic Cochrane Centre, Rigshospitalet, Denmark
Tom Jefferson, Honorary Research Fellow, Centre for Evidence Based Medicine, Oxford, UK
Margrete Auken, MEP (The Greens/European Free Alliance)
Louise Brinth, PhD, MD, Danish Syncope Unit, Frederiksberg, Denmark
3